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Using imaging and multiplex bead\u2010based flow cytometry, we comprehensively quantified circulating EVs with respect to their cellular origin in a large cohort of healthy blood donors. We assessed coefficients of variations to characterize their biological variation and explored demographic, clinical, and lifestyle factors contributing to observed variation. Cell\u2010specific circulating EV subsets show a wide range of concentrations that do not correlate with cell\u2010of\u2010origin concentrations in blood, suggesting steady\u2010state EV subset concentrations are regulated by complex mechanisms, which differ even for EV subsets from the same cell type. Interestingly, tetraspanin+ circulating EVs largely originate from platelets and to a lesser extent from lymphocytes. 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