INTRODUCTION: More than 100 million people have been infected worldwide by the SARS-COV-2 virus, which is responsible for an acute disease called COVID-19. Multiple studies have shown how various symptoms in these patients can persist for several months after resolution of the acute process, known as post-COVID syndrome. The neurological clinic is varied, but with constant presentation of fatigue. OBJECTIVE: Analyze post-COVID fatigue. METHODS: We present a single-center, prospective, case-COntrol study comparing patients with fatigue in the context of a post-COVID syndrome with patients who have passed COVID-19 without post-COVID fatigue. A baseline record (April 2021) and a control record at 6 months were made. Clinical variables, fatigue questionnaires, sleep disorders, depression, anxiety, cognitive impairment and quality of life are recorded. Basic analyzes of the 2 visits are collected. In addition, a substudy of inflammatory (IL-6, IL-1β, TNF-α) and anti-inflammatory (IL-10) cytokines is performed. RESULTS: The fatigue of the patients measured by Chadler is of moderate and mixed intensity (physical and psychological). At 6 months, physical fatigue improves, but psychological fatigue does not. Significant differences were found in sleepiness, cognitive deterioration, anxiety and quality of life. Significant alterations are evident of TNF-α values, but not in the rest of the cytokines. CONCLUSIONS: Patients with fatigue have a poorer quality of life, with improvement in control being observed at 6 months, which suggests a course that could be self-limiting, but this will have to be confirmed with longer studies.