Rationale: Sepsis is an archetypal condition with molecular links between inflammation and coagulation. Both events can be orchestrated by the interaction between circulating and vascular cells that under activation release microparticles. Objectives: We characterised circulating microparticles from both non-septic and septic shock subjects and evaluated their contribution on vascular function. Methods: Circulating microparticles and their cell origin were measured in blood from 36 patients with septic shock and 18 non-septic subjects by flow cytometer. Then, microparticles were injected i.v to mice and vascular reactivity was assessed in aorta. Expression and activity of enzymes involved in nitric oxide and cyclooxygenase metabolites production were analyzed. Results: Circulating levels of microparticles, platelet- and endothelial-derived microparticles were increased in septic patients. Surprisingly, septic microparticles enhanced but not reduced sensitivity of contraction of mouse aortas in response to serotonin. Interestingly, septic microparticles enhanced contraction of aortas from lipopolysaccharide-treated mice. This effect was linked neither to increased calcium entry nor Rho-kinase inhibitor-sensitive mechanisms. Besides, the effect of septic microparticles was not modified either by NO-synthase or cyclooxygenase-2 inhibitors, and was not associated with NO or O₂^- overproduction. The non-selective cyclooxygenase-2 inhibitor, indomethacin, and the specific thromboxane A₂ antagonist, SQ-29548, either reduced or abolished contraction in aorta from mice treated with non-septic and septic microparticles, respectively. The effect of septic microparticles was associated with an increased thromboxane A₂ production, and was sensitive to a selective thromboxane A₂ antagonist. Conclusion: We provide evidence that increased circulating microparticles are protective against vascular hyporeactivity accounting for hypotension in patients with septic shock.