Objective. Characterization of the abundance, origin, and annexin V (AnxV)-binding capabilities of circulating microparticles (MPs) in SLE patients and healthy controls and to determine any associations with clinical parameters. Methods. Seventy unselected SLE patients and 29 sex-and age-matched healthy control subjects were included in the study. MPs were isolated from citratetreated plasma and characterized by flow cytometry using AnxV or antibodies to platelet, leukocyte, or endothelial cell surface markers. Results. SLE patients had significantly increased concentrations of AnxV-nonbinding (AnxV؊) MPs (P < 0.0001), while the concentrations of total MPs (P ؍ 0.011) and AnxV-binding (AnxV؉) MPs (P < 0.0001) were decreased, as compared with controls. Based on flow cytometric characteristics, 2 subgroups of AnxV؊ MPs could be discerned: AnxV؊ cell-derived MPs (CDMPs) and AnxV؊ MPs of unknown nature (UNMPs). Both fractions were significantly increased in SLE patients (P ؍ 0.007 and P ؍ 0.0018, respectively). Platelet-and leukocyte-derived MPs were decreased in the SLE patients (P < 0.0001), whereas no difference was observed for endothelial cell-derived MPs (P ؍ 0.14). The concentrations of AnxV؊ CDMPs correlated with the concentrations of endothelial cell-derived MPs, the disease activity score, active nephritis, hypertension, history of arterial thrombosis, and triglyceride levels (P < 0.05 for all comparisons). Conclusion. The concentrations and composition of MPs in SLE patients differ markedly from those in healthy subjects. Overall MP numbers were significantly decreased, but two distinct subpopulations of AnxV؊ MPs were significantly increased. These findings call for further characterization of MPs in SLE patients to elucidate their role in disease pathogenesis.