Blood plasma derived extracellular Vesicles (EVs) could be important in mediating cell-to-cell-contact and thereby induce functional changes in targeted cell. This might help to understand pathomechanisms of disease such as post-infectious Myalgic Enceplhalomyelitis /Chronic Fatigue Syndrome (ME/CFS). This chronic disease with higher prevalence in females is mainly induced by viral infections and also by SARS-CoV2 and the diagnostic options are still very limited. Therefore, the cargo of EVs such as proteins and different small RNAs might serve as a potential useful diagnostic tool. In this study we aimed to improve disease diagnosis for post-COVID 19 ME/CFS by identifying new protein markers in the cargo of plasma derived EVs from a female patient group in comparison to a matched healthy donor group.