BACKGROUND: Multiple sclerosis is the one of leading causes of non-traumatic disability in young adult patients. An in-depth understanding of the processes of neuroplasticity underlying rehabilitation measures will ensure full and effective recovery of patients with this disease. AIM: To evaluate changes in the brain connectome in patients with multiple sclerosis in response to complex rehabilitation. MATERIALS AND METHODS: A prospective cohort study included 20 patients with relapsing-remitting multiple sclerosis (EDSS 1.5–6.5) in remission. All patients underwent comprehensive inpatient neurorehabilitation in a volume corresponding to individual rehabilitation needs for 5 weeks. To assess changes in the connectome, resting-state functional magnetic resonance imaging (rs-fMRI) was performed at three points: before the start of rehabilitation, immediately after its completion, and one month after discharge from the hospital. Statistical analysis is carried out using the CONN 7 (based on MathLab). Clinical neurological examination included examination using functional tests, passing questionnaires, and determining scores on the EDSS scale before and after rehabilitation. RESULTS: A total of 20 patients were examined, 13 of them at three control points. According to rs-fMRI data, clusters of decreased connectivity were identified between the left parahippocampal gyrus and the lateral cortex of the right occipital lobe, and between the right parahippocampal gyrus and the precuneus (p-FWE, p-FDR of cluster size and mass