The World Health Organization (WHO) defines post-coronavirus disease 2019 (COVID-19) as a condition which occurs in individuals with a history of probable or confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection 3 months after the onset of COVID-19 symptoms, lasts for at least 2 months and cannot be explained by an alternative diagnosis. Core symptoms of post-COVID syndrome are fatigue, dyspnea and cognitive dysfunction, which have an impact on everyday functional level. Neuropsychiatric late sequelae are common in COVID-19 patients, with incidence rates over 30%. Beside the abovementioned core symptoms, sleep disorders, depression and anxiety show increased incidences. According to current opinion, associated neuropsychiatric symptoms are subsumed under the term post-COVID syndrome but are also interpreted as comorbidities, which can promote the manifestation of a post-COVID syndrome. The key symptom fatigue shows symptom overlapping and comorbidity with psychiatric disorders. Imaging studies indicate an organic correlate of fatigue in post-COVID patients. Furthermore, psychosocial aspects and psychiatric comorbidities, such as depression and anxiety disorders as modulating and therefore potentially treatable factors were identified. Treatment of fatigue consists of pharmacological management with stimulants and antidepressants as well as nonpharmacological strategies, most notably cognitive behavioral therapy and exercise-focused interventions. The evidence for this comes from meta-analyses of tumor-associated or post-viral fatigue.