Blood Tests for Fatigue: A GP's Guide to What to Check

Fatigue is one of the most common reasons people visit their GP, and one of the hardest to investigate. The list of possible causes is long. You might be told to get more sleep, reduce stress, or that your blood tests are "normal". But in many cases, the right blood tests haven't been done, or the results haven't been interpreted with enough clinical depth.

This article is a practical guide to the blood tests that are genuinely useful when fatigue is your primary symptom. Not everything on this list will apply to you. But understanding which markers are worth checking, and why, gives you the knowledge to have a more useful conversation with your doctor.

Why Fatigue Is Difficult to Investigate

Fatigue is a symptom, not a diagnosis. It can be caused by iron deficiency, depression, an underactive thyroid, undiagnosed diabetes, and dozens of other conditions. In primary care, fatigue accounts for roughly 10 to 20 percent of all GP consultations. But a specific diagnosis is reached in fewer than half of those patients, and a purely physical cause (such as anaemia or thyroid disease) is found in only around 4 to 5 percent of cases [Stadje et al., BMC Family Practice, 2016]. The rest is often a mix of psychological, lifestyle, and unexplained factors.

But targeted blood testing is still essential. When a treatable physical cause is present, it's often one of the most straightforward problems to address.

Core Blood Tests to Consider for Fatigue

When a patient presents with unexplained, persistent fatigue, here is the panel I consider. Each test targets a different mechanism that can cause or contribute to tiredness.

• Full blood count (FBC) is the starting point. This measures haemoglobin, red blood cells, white blood cells, and platelets. Low haemoglobin indicates anaemia. A raised MCV (mean corpuscular volume) might suggest B12 or folate deficiency. A low MCV might point toward iron deficiency even before haemoglobin drops.

• Ferritin is a critical marker in any fatigue investigation. It measures your body's iron stores. You can have a normal haemoglobin and a completely depleted ferritin. Many laboratories flag ferritin as "normal" above 15 µg/L, but the British Society of Gastroenterology defines iron deficiency as ferritin below 30 µg/L [BSG, Gut, 2021]. Some clinicians find that fatigue often persists until ferritin rises above 50 µg/L, and a small 2012 randomised controlled trial suggested that iron supplementation improved fatigue in non-anaemic women with ferritin below 50 µg/L [Vaucher et al., CMAJ, 2012]. One important caveat: ferritin is an acute-phase reactant, which means it rises during infection or inflammation. If your CRP is elevated, a "normal" ferritin doesn't necessarily rule out iron deficiency.

• Thyroid function (TSH, free T4, free T3) Thyroid disease is one of the most common treatable causes of fatigue, affecting an estimated 5% of the UK population [British Thyroid Foundation]. TSH is the main screening test. If it comes back abnormal, free T4 is added to assess how much active hormone is circulating. Free T3 is not usually part of a routine fatigue workup - it's more relevant when hyperthyroidism is suspected. If TSH is raised, thyroid peroxidase antibodies (anti-TPO) can help confirm whether the underlying cause is autoimmune, as in Hashimoto's thyroiditis.

• Vitamin D deficiency remains common in the UK. The latest National Diet and Nutrition Survey found that 18% of adults aged 19 to 64 had levels below 25 nmol/L, the threshold associated with poorer bone and muscle health [NDNS, 2019–2023]. Deficiency is most likely after winter, because UK sunlight is only sufficient for skin synthesis from late March or early April through to September [SACN, 2016]. Low vitamin D can contribute to fatigue, muscle weakness, bone pain, and low mood, but it is rarely the whole explanation on its own.

• Vitamin B12 and folate are worth checking in any fatigue workup. B12 deficiency causes fatigue, brain fog, and neurological symptoms. It's particularly common in vegetarians, vegans, older adults, and people taking proton pump inhibitors or metformin. NICE guidance (NG239, 2024) indicates that a total B12 below 180 ng/L (133 pmol/L) generally supports a diagnosis of deficiency, while levels between 180 and 350 ng/L fall into an indeterminate zone where clinical judgement and sometimes further testing are needed. Symptoms can occur even when levels sit within that grey area.

• HbA1c measures average blood sugar over two to three months. Fatigue is one of the earliest symptoms of impaired glucose regulation. An HbA1c between 42 and 47 mmol/mol indicates non-diabetic hyperglycaemia (commonly called pre-diabetes), a reversible window most people never know they're in [NICE PH38, 2012].

• Liver and kidney function tests are part of the baseline. Liver disease often causes fatigue before any other symptoms appear. Kidney function markers (urea, creatinine, eGFR) can detect chronic kidney disease, which is frequently asymptomatic in its early stages.

• CRP and ESR are markers of inflammation. They're not specific, but they can flag that something systemic is going on. Elevated inflammatory markers in someone with persistent fatigue may prompt investigation into autoimmune conditions, chronic infections, or other underlying disease.

• Coeliac serology (tissue transglutaminase antibodies, or tTG) is worth including. Coeliac disease is underdiagnosed and can present with fatigue, iron deficiency, or both, sometimes without any obvious gut symptoms. NICE recommends coeliac screening as part of the investigation for persistent fatigue (NG20, 2015). Coeliac blood tests are only reliable if you are still eating gluten regularly before testing, so do not start a gluten-free diet before being tested.

When Multiple Causes Overlap

One of the things I see regularly in practice is fatigue caused by more than one factor at the same time. A woman might have low ferritin, borderline thyroid function, and vitamin D deficiency. None of them individually looks dramatic on a lab report. Together, they explain why she feels exhausted.

This is why checking a broad panel matters more than testing one or two markers in isolation. And it's why the interpretation matters as much as the numbers themselves. A ferritin of 18 might be flagged as "normal" by the lab, but in a young woman with heavy periods and persistent fatigue, it's not normal. It's very likely a major contributing factor.

I also see patients whose fatigue has a clear biochemical component alongside lifestyle factors like poor sleep or chronic stress. Addressing the blood test abnormality doesn't always resolve the fatigue entirely, but it removes a layer that was making everything worse. That's still worth doing.

When to See Your GP

See your GP if your fatigue has persisted for more than four weeks without an obvious explanation, if it is getting progressively worse, or if it is accompanied by other symptoms such as unexplained weight loss, night sweats, persistent pain, or changes in bowel habit. You should also seek advice if fatigue is significantly affecting your ability to work, exercise, or function normally.

The NICE guideline on ME/CFS (NG206, 2021) recommends that when the characteristic symptom pattern has persisted for six weeks or more in adults, with reduced day-to-day function, clinicians should investigate to exclude other diagnoses. The recommended investigations include a full blood count, kidney function, liver function, thyroid function, inflammatory markers, HbA1c, ferritin, coeliac serology, and creatine kinase.

How Brooksby Medical Can Help

Brooksby Medical offers a Nutrients and Energy Profile that covers the key markers linked to energy production: iron, ferritin, B12, folate, and vitamin D. For a broader investigation, the Wellness Profile combines ferritin with a full metabolic health screen across eleven markers including thyroid function, HbA1c, liver function, and kidney function. We also off a coeliac screen.

Every result comes with a GP-written report that explains not just whether your results are within the reference range, but what they mean in context. That includes the patterns that might be missed if each marker is viewed in isolation.

If you've been told your blood tests are normal but you still feel exhausted, it may be worth checking whether the right tests were done in the first place.

References

1. Stadje R, Dornieden K, Baum E, et al. The differential diagnosis of tiredness: a systematic review. BMC Family Practice. 2016;17:147

2. Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut. 2021;70(11):2030-2051

3. Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin. CMAJ. 2012;184(11):1247-1254

4. Scientific Advisory Committee on Nutrition (SACN). Vitamin D and Health. 2016. SACN Report

5. Public Health England / Food Standards Agency. National Diet and Nutrition Survey: Years 9-11. NDNS 2020

6. NICE. Vitamin B12 deficiency in over 16s: diagnosis and management. Guideline NG239 (2024). NICE NG239

7. NICE. Type 2 diabetes: prevention in people at high risk. Public health guideline PH38 (2012, updated 2023). NICE PH38

8. NICE. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. Guideline NG206 (2021). NICE NG206

9. British Thyroid Foundation. Thyroid disorders: prevalence and general information. BTF

Written by Dr James Coleman, GP and founder of Brooksby Medical. Dr Coleman is a practising General Practitioner who founded Brooksby Medical to give patients direct access to the blood tests and clinical interpretation they need, without waiting lists.

Medically reviewed: March 2026 | Next review due: March 2027

Medical disclaimer: This article is for informational purposes only and does not constitute medical advice. Blood test results should always be interpreted by a qualified healthcare professional in the context of your individual symptoms, medical history, and clinical picture. If you have concerns about your health, please consult your GP.