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Fatigue is anecdotally one of the most commonly reported and disabling symptoms after COVID-19. Furthering our knowledge concerning differences and similarities in genesis and patho-physiological mechanisms seems to be the most promising approach in order to tailor assessment and effective treatment. In the present study we jointly investigate immunological, nutritional, psychological and neurological (brain network connectivity) mechanisms comparing patients with post-COVID syndrome with patients with mylagic encephalomyelitis/chronic faitigue syndrome (ME/CFS), exhaustion disorder (ED), and healthy controls. Our hypothesis is that there are shared biopsychosocial vulnerability factors to develop and maintain fatigue, irrespective of the main diagnosis. We also hypothesise that there are subgroups that differ in terms of these factors. This study is based on an ongoing cohort on fatigue in Stockholm (ClinicalTrials.gov NCT04955587) and a sister study starting up in Linköping during 2021. Patients with post-COVID fatigue, ME/CFS and ED are being followed for 24 months with blood samples for peripheral biological markers and questionnaire reports at baseline and month 1, 2, 4, 6, 12, 18 and 24. In addition, an fMRI investigation, and urine metabolic test and a 3-day diet registration are performed at one time point. The long-term goals with the project include improved health-care and consequently improved functioning, health and quality of life for affected patients.