INTRODUCTION: Owing to the novelty of COVID-19, there are still large knowledge gaps concerning its effect on the brain and the resulting impact on peoples' lives. This large-scale prospective follow-up study investigates COVID-19-associated brain damage, neuropsychological dysfunction and long-term impact on the well-being of patients and their close ones. It is hypothesised that structural brain damage and cognitive dysfunction primarily occur in severely ill patients, as compared with moderately ill patients. Cognitive complaints, emotional distress and impact on well-being are hypothesised to be less dependent on illness severity. METHODS AND ANALYSIS: For this multicentre study, 200 patients with COVID-19 (100 intensive care unit (ICU) patients and 100 non-ICU patients) formerly hospitalised in one of the six recruiting hospitals during the first European infection wave (ie, March to June 2020) and their close ones will be recruited. At minimally 6 months posthospital discharge, patients will perform a set of neuropsychological tests and are subjected to a 3T MRI scan. Patients and close ones will fill out a set of questionnaires, also at minimally 6 months posthospital discharge and again another 6 months thereafter. Data related to COVID-19 hospitalisation will be extracted from the patients' medical records. MRI abnormalities will ultimately be related to neuropsychological test performance and questionnaire outcomes. ETHICS AND DISSEMINATION: Ethics approval was granted by the medical research ethics committee of Maastricht University Medical Centre and Maastricht University (NL75102.068.20). The project is sponsored by The Brain Foundation Netherlands. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04745611.