Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend thedisease’s pathogenesis iscrucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease’s pathological processes.This study aimed to identify the immune and nervous system-associated EV profile in blood that could have a specific role as biomarker in MS. We also assessed the possible correlation between this EV profile with disease activity and cognitive and motor dysfunction in patients with MS. For this propose, we analyzed the levels, diameter and protein content of circulating nervous and immune system-derived EVs in the blood of patients with MS compared to the EVs found in another immune-mediated disease (rheumatoid arthritis) and in another white matter lesion (subcortical stroke) to determine the contribution of these EVs to autoimmunity and brain damage.