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Blood Test for Fatigue: What Your Doctor Should Order

Constantly tired and wondering if there's a medical cause? Learn which blood tests can help identify the root cause of fatigue, from anemia to thyroid problems and beyond.

W
WellAlly Medical Team
2025-12-20
9 min read

You're tired. Not just "I need another cup of coffee" tired, but exhausted in a way that sleep doesn't fix. You're wondering: Could there be a medical reason? Should you get blood tests? What tests actually matter for fatigue?

This guide will explain which blood tests can help identify the medical causes of fatigue, what each test checks for, and how to advocate for thorough testing when you see your doctor.

Quick Reference: The Fatigue Blood Test Panel

Test CategorySpecific TestsWhat It Checks For
Anemia screeningCBC, ferritin, iron panelIron deficiency, B12/folate deficiency, other anemias
Thyroid functionTSH, free T4Hypo-/hyperthyroidism
MetabolicGlucose, HbA1cDiabetes, blood sugar issues
Organ functionCMP (liver, kidney)Liver or kidney disease
InflammationCRP, ESRChronic inflammation, infection
NutritionalVitamin D, B12, folateDeficiencies that cause fatigue
AutoimmuneANA, RF, othersAutoimmune conditions
InfectionMono test, Lyme, othersSpecific infections

Why You're Tired: The Medical Causes of Fatigue

Fatigue is one of the most common reasons people see doctors, and there are many potential medical causes. The good news is that most are identifiable with simple blood tests.

Common Medical Causes of Fatigue

CategorySpecific ConditionHow It Causes Fatigue
AnemiaIron deficiency, B12 deficiencyNot enough oxygen-carrying capacity
ThyroidHypothyroidismSlowed metabolism
DiabetesHigh or low blood sugarCells not getting energy properly
InfectionsMono, Lyme, COVIDImmune system using energy to fight
AutoimmuneLupus, RA, MSChronic inflammation
NutritionalVitamin D, B12 deficiencyEssential for energy production
Organ dysfunctionLiver, kidney, heartBody not working efficiently
HormonalMenopause, low testosteroneHormonal imbalance
Sleep disordersSleep apneaPoor quality sleep
Depression/anxietyMental healthBrain chemistry changes

The Essential Fatigue Blood Work

1. Complete Blood Count (CBC)

The CBC is the starting point for any fatigue workup. It measures:

ComponentWhat It IsWhat Abnormal Results Mean
HemoglobinOxygen-carrying proteinLow = anemia
HematocritPercentage of red blood cellsLow = anemia
MCVRed blood cell sizeHelps determine anemia type
WBCWhite blood cellsHigh = infection/inflammation
PlateletsClotting cellsAbnormal = various conditions

What it finds:

  • Anemia (low hemoglobin/hematocrit)—the most common medical cause of fatigue
  • Infection (high white blood count)
  • Signs of bone marrow problems

2. Iron Studies

If CBC suggests anemia or you're at risk, iron studies help determine the type:

TestWhat It ShowsPattern in Iron Deficiency
FerritinIron storesLow
Serum ironIron in bloodLow
TIBCIron-binding capacityHigh
Transferrin saturation% of binding sites filledLow

Who should get this:

  • Women with heavy periods
  • Vegetarians/vegans
  • Pregnant women
  • Anyone with fatigue and low hemoglobin

3. Thyroid Function Tests

Thyroid problems are incredibly common and a major cause of fatigue.

Essential tests:

  • TSH (thyroid stimulating hormone): The screening test
  • Free T4: The active thyroid hormone

Pattern:

TestHypothyroidismHyperthyroidism
TSHHighLow
Free T4LowHigh

Additional tests (if TSH is abnormal):

  • Free T3
  • Thyroid antibodies (TPO, thyroglobulin)

Who should get this:

  • Anyone with unexplained fatigue
  • Women over 60
  • Anyone with a family history of thyroid disease
  • Anyone with other thyroid symptoms (weight changes, temperature sensitivity, hair loss)

4. Comprehensive Metabolic Panel (CMP)

This panel checks multiple organ systems:

ComponentWhat It ChecksFatigue Connection
GlucoseBlood sugarDiabetes can cause fatigue
Liver enzymes (ALT, AST)Liver healthLiver disease causes fatigue
Kidney tests (creatinine, BUN)Kidney functionKidney disease causes fatigue
Electrolytes (sodium, potassium)Mineral balanceAbnormalities cause weakness
CalciumCalcium levelAbnormalities affect energy

Who should get this:

  • Anyone with fatigue plus other symptoms
  • Anyone over 40 (baseline screening)
  • Anyone on long-term medications

5. Vitamin D

Vitamin D deficiency is incredibly common and causes significant fatigue.

Who's at risk:

  • Indoor workers
  • People in northern climates
  • People with darker skin
  • Older adults
  • People who are overweight

Severe deficiency (< 12 ng/mL) causes:

  • Bone pain
  • Muscle weakness
  • Significant fatigue

Moderate deficiency (12-20 ng/mL) can cause:

  • Low energy
  • Mood changes
  • Poor sleep

6. Vitamin B12 and Folate

Deficiencies cause anemia and directly affect energy levels.

Who's at risk for B12 deficiency:

  • Vegans/vegetarians (B12 is only in animal products)
  • People over 50 (absorption decreases with age)
  • People on acid-suppressing medications (PPIs)
  • People who've had gastric bypass
  • People with pernicious anemia (autoimmune)

Who's at risk for folate deficiency:

  • Pregnant women
  • People with poor diet
  • People with malabsorption conditions
  • Heavy alcohol users

The "Second-Line" Tests

If initial testing is normal but you're still exhausted, your doctor might order:

Inflammation Markers

  • CRP (C-Reactive Protein): General inflammation marker
  • ESR (Erythrocyte Sedimentation Rate): Another inflammation marker

Elevated levels suggest:

  • Autoimmune conditions (lupus, RA)
  • Chronic infections
  • Inflammatory conditions

Autoimmune Screening

  • ANA (Antinuclear Antibody): Screens for autoimmune diseases like lupus
  • RF (Rheumatoid Factor): Screens for rheumatoid arthritis
  • Others as clinically indicated

Infection-Specific Tests

If your story suggests a specific infection:

  • Monospot: Mononucleosis
  • Lyme antibodies: Lyme disease
  • Viral hepatitis panel: If liver enzymes elevated
  • HIV test: If risk factors present
  • TB testing: If relevant exposure

Hormone Tests

For women:

  • FSH, LH, estrogen, progesterone: Menopause, PCOS
  • Prolactin: If relevant symptoms

For men:

  • Testosterone: Low testosterone causes fatigue

Cortisol

If your fatigue is worse in the mornings and you have other symptoms, your doctor might check for adrenal issues. However, true adrenal insufficiency is rare.

Tests You Might Consider Asking About

These tests aren't always part of a standard workup but can be valuable:

1. Reverse T3

Some doctors check reverse T3 in people with hypothyroid symptoms but normal TSH. The theory is that stress or illness can convert T4 to inactive reverse T3 instead of active T3.

2. Cortisol Saliva Test

Measures cortisol throughout the day. Some practitioners use this to assess adrenal function, though the evidence for "adrenal fatigue" as a diagnosis is controversial.

3. Food Sensitivity Testing

Controversial, but some people find relief by identifying foods that cause inflammation.

4. Mold Toxin Testing

If you've been exposed to water-damaged buildings, some practitioners test for mycotoxins. This is not mainstream but may be relevant for some people.

5. Heavy Metal Testing

If you've had exposure, heavy metal testing may be appropriate.

When Tests Are Normal: What Next?

It's frustrating when you're exhausted but all your tests are normal. This actually happens fairly often. What then?

Consider These Possibilities:

1. Sleep Disorders

  • Sleep apnea: Very common, very underdiagnosed
  • Restless leg syndrome
  • Insomnia: Poor sleep quality

Ask for a sleep study if you snore, wake up gasping, or are still tired after a full night's sleep.

2. Mental Health

  • Depression: Can cause significant fatigue even without sadness
  • Anxiety: Constant worry is exhausting
  • Burnout: Prolonged stress

Therapy and/or medication can help significantly.

3. Lifestyle Factors

  • Poor diet
  • Lack of exercise (ironically, being sedentary causes fatigue)
  • Caffeine dependence (withdrawal causes fatigue)
  • Alcohol use (disrupts sleep quality)
  • Dehydration

4. Chronic Fatigue Syndrome / ME A diagnosis of exclusion—when all other causes are ruled out. Characterized by:

  • Fatigue that worsens with activity
  • Sleep that doesn't refresh
  • Other symptoms like brain fog, swollen lymph nodes, sore throat

5. Long COVID Fatigue is one of the most common long COVID symptoms, lasting months after infection.

How to Advocate for Thorough Testing

Doctors have limited time and may not order every test upfront. Here's how to advocate for yourself:

Before Your Appointment

  1. Track your symptoms: When is fatigue worse? What helps? What other symptoms do you have?
  2. List your medications: Everything you take
  3. Family history: Thyroid problems? Anemia? Autoimmune disease?
  4. Timeline: When did fatigue start? Gradual or sudden?

During Your Appointment

  1. Be specific about how fatigue affects you:

    • "I'm too tired to exercise"
    • "I need a nap every day"
    • "I'm falling asleep at work"
    • "I don't have energy to spend time with family"
  2. Ask specifically about tests:

    • "I'd like to rule out anemia and thyroid problems"
    • "Could we check my vitamin D and B12?"
    • "Is there anything else that could explain my fatigue?"
  3. Don't accept "it's just stress" without testing:

    • Stress can certainly cause fatigue
    • But medical causes should be ruled out first
    • You can have both stress AND a medical issue

If Testing Is Normal But You're Still Exhausted

  1. Ask what's next: "What should we do if these tests are normal?"
  2. Request a follow-up: "When should we recheck if I'm not better?"
  3. Ask about referrals: "Should I see a specialist?"
  4. Consider a second opinion: If you feel dismissed

Questions to Ask Your Doctor

  1. "What tests are you ordering to evaluate my fatigue?"
  2. "Could you explain what each test is checking for?"
  3. "What happens if these tests are normal?"
  4. "Should I see a specialist (endocrinologist, rheumatologist, etc.)?"
  5. "Could my symptoms be from more than one cause?"
  6. "Are there any tests you're NOT ordering that might be helpful?"
  7. "When should I expect to feel better?"
  8. "What lifestyle changes do you recommend while we figure this out?"
  9. "Should I keep a symptom diary?"
  10. "Is there anything that would make you re-evaluate your diagnosis?"

Special Situations

Fatigue in Women

Women are at higher risk for:

  • Iron deficiency (from menstruation, pregnancy)
  • Thyroid problems (5-8x more common than men)
  • Depression (diagnosed more often in women)

Make sure your doctor checks iron stores (ferritin) even if your CBC is normal—early iron deficiency shows up as low ferritin before anemia develops.

Fatigue After COVID-19

Long COVID fatigue is common. If you had COVID-19 and your fatigue started afterward:

  • Consider a long COVID clinic
  • Gradual return to activity ( pacing)
  • Some people benefit from specific rehabilitation programs

Fatigue in Older Adults

In older adults, fatigue is sometimes dismissed as "just getting older." This is wrong. Older adults deserve the same thorough evaluation. In fact, some causes are MORE common in older adults:

  • Anemia
  • Thyroid problems
  • Vitamin B12 deficiency
  • Medication side effects

The Bottom Line

Fatigue has many potential medical causes, and most can be identified with simple blood tests. The key is getting comprehensive testing and not accepting "everything's normal" without understanding what was actually checked.

Essential fatigue testing includes:

  • CBC (for anemia)
  • Iron studies (if anemia or at risk)
  • TSH and free T4 (thyroid)
  • CMP (organ function, glucose)
  • Vitamin D
  • Vitamin B12 and folate

If initial testing is normal:

  • Consider sleep disorders
  • Screen for depression/anxiety
  • Evaluate lifestyle factors
  • Consider chronic fatigue syndrome
  • Keep advocating for yourself

Remember: You know your body best. If you're exhausted and it's affecting your life, you deserve thorough evaluation to find the cause. Fatigue isn't "just in your head"—there's almost always a reason, whether medical, psychological, or lifestyle-related. Keep pushing until you get answers.


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