Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by post-exertional malaise, fatigue and pain. Yet, its underlying biological mechanisms remain poorly understood. Extracellular vesicles (EVs) are nanoparticles carrying biological cargo and are involved in cell-cell communication. Plasma EVs reflect several disease states and may serve as minimally invasive biomarkers. We characterized the plasma EV profiles of ME/CFS patients (N=49) and healthy controls (N=50), by enriching for EVs by size-exclusion chromatography coupled to high-resolution quantitative proteomics.