Which Blood Tests for Fatigue? 14 Lab Markers a GP Should Check

Dr. Charalampos Romanos, General Practitioner (Swiss FMH) · Published: 21 May 2026 · Medically reviewed: 21 May 2026 · 7 min read

When patients come in with chronic fatigue, the first question is almost always the same: "Which blood tests should we actually run?" A standard full blood count is rarely enough. Here is the structured panel I use at my GP practice next to Zurich main station — organised by the medically most common causes.

1. Full blood count — the baseline, rarely the full answer

A complete blood count (haemoglobin, red and white cells, MCV, MCH, platelets) gives a first impression: is there anaemia? Are inflammatory markers visible? Any signs of a haematological condition? I regularly see patients with significant fatigue and a completely normal blood count — which is why it is only the starting point.

2. Ferritin — the single most important marker

Ferritin reflects iron stores. A value below 30 µg/L can already cause fatigue, poor concentration, hair loss, and restless legs — even when haemoglobin is still in the normal range. This pattern is called iron deficiency without anaemia, and it is especially common in premenopausal women, female athletes, vegetarians, and during pregnancy.

Important: ferritin is also an acute-phase reactant. During inflammation it rises and can mask iron deficiency. When the picture is unclear we add transferrin saturation and CRP.

3. TSH, fT3, fT4 — the thyroid

An underactive thyroid (hypothyroidism) classically causes fatigue, cold intolerance, weight gain, and low mood. Often missed is subclinical hypothyroidism: an elevated TSH with still-normal fT3/fT4 — a pre-stage that can already produce symptoms. Where autoimmune disease (Hashimoto's thyroiditis) is suspected we add the antibodies anti-TPO and anti-Tg.

4. Vitamin D (25-OH) — low in over half of my patients

In Zurich, more than 60% of my patients — particularly between November and April — have a vitamin D level under 30 ng/mL. Vitamin D affects not only bone health but also muscle function, the immune system, and energy. The target range is 30–60 ng/mL (75–150 nmol/L).

5. Vitamin B12 — but specifically active B12

Total B12 (cobalamin) is the standard value — but it is imprecise. Holotranscobalamin (active B12) is more meaningful, as it measures only the fraction actually available to cells. B12 deficiency is particularly common in vegetarians and vegans, in patients on proton pump inhibitors (PPI) or metformin, and in older adults — and can cause fatigue, poor concentration, tingling, and mood changes.

6. Folate — B12's counterpart

Folate (vitamin B9) works alongside B12 in blood formation and methylation metabolism. Isolated folate deficiency is less common, but worth checking in fatigue — especially in pregnancy, with alcohol use, or on certain medications (methotrexate, antiepileptics).

7. HbA1c and fasting glucose — the glucose axis

Fatigue after meals, afternoon energy crashes, sugar cravings — these can be early signs of insulin resistance, long before manifest diabetes develops. HbA1c shows long-term blood glucose over the last three months; fasting glucose reflects the current level. Where clinically indicated we add fasting insulin and calculate the HOMA index as a measure of insulin sensitivity.

8. CRP — is there hidden inflammation?

Chronic low-grade inflammation (silent inflammation) can present clinically only as fatigue and lack of drive. A high-sensitivity CRP (hs-CRP) provides clues. If persistently elevated, we look further — teeth, gut, chronic infections, autoimmune disease.

9. Liver enzymes (ALT, AST, GGT)

Fatty liver (often asymptomatic) is now the most common abnormal liver finding in Switzerland and can contribute to fatigue. Hidden alcohol use, drug side effects, or hepatitis can also present primarily as fatigue. ALT, AST, and GGT are the standard panel — where abnormal we add bilirubin, alkaline phosphatase, and depending on suspicion a hepatitis serology.

10. Creatinine and eGFR — kidney function

Impaired kidney function causes fatigue, loss of appetite, and concentration problems — often insidiously, without patients noticing. Creatinine alone is imprecise (it depends on muscle mass), so we calculate the eGFR (estimated glomerular filtration rate).

11. Electrolytes — sodium, potassium, calcium, magnesium

Electrolyte shifts are an underestimated cause of fatigue, muscle weakness, cramps, and rhythm disturbances. Magnesium deficiency in particular often presents only as diffuse fatigue. When measuring magnesium, note that serum magnesium reflects only a small fraction of total body magnesium — if symptoms persist despite a normal serum value, intracellular (whole-blood) magnesium can be added.

12. Salivary cortisol day-curve — when the stress axis is suspected

Persistent stress can shift the cortisol pattern: tired in the morning, afternoon energy slump, restless in the evening. A single morning cortisol is not enough here — we use a salivary cortisol day-curve (4 measurement points across the day) for a reliable assessment of the hypothalamic-pituitary-adrenal (HPA) axis.

13. Sex hormones — depending on history

In women in perimenopause or postmenopause, falling oestrogen and progesterone are a common cause of fatigue, sleep disturbance, and mood changes. In men from middle age onward, testosterone (total and free) should be checked — low values can equally cause chronic fatigue. Indication depends on age, history, and symptoms.

14. Optional extensions where indicated

Depending on history and clinical picture we selectively add: coeliac antibodies (anti-tissue transglutaminase) for digestive symptoms, EBV serology after a recent infection, ANA / rheumatoid factor where autoimmune disease is suspected, a lipid panel for cardiovascular context, homocysteine where methylation is in question, or an amino-acid profile when neurotransmitter imbalance is suspected.

When to see a doctor about fatigue

If fatigue lasts longer than 4 weeks, significantly limits your ability to function, or comes with other symptoms — unintended weight change, hair loss, dizziness, shortness of breath, persistent pain — it belongs in a doctor's hands. A structured GP work-up with labs and a thorough history saves you long detours and delivers a clear medical assessment.

What we do in the practice

At my GP practice next to Zurich main station, fatigue starts with a structured check-up covering the baseline panel. If findings remain unclear, we deepen the work-up under our Extended Diagnostics programme — thyroid antibodies, active B12, salivary cortisol curve, and targeted specialist values. Where deficiencies are documented, we may add IV therapy (iron, vitamin C, B-complex) for faster repletion.