Recent studies have shown that patients with antiphospholipid antibodies (aPL) have increased lipid peroxidation. We evaluated the urinary excretion of 11-dehydro thromboxane B2 (11-DH-TXB(2) and isoprostane F(2alpha)III (IPF(2alpha)III), reflecting platelet activation and lipid peroxidation in vivo, and plasma soluble markers of endothelial cell, platelet and blood coagulation activation: soluble vascular cell adhesion molecule-1 (sVCAM-1), P- and E-selectin (sPsel and sEsel), F1 + 2 fragment of prothrombin (F1 + 2), thrombin-antithrombin complexes (TAT) and D-Dimer (DD). We studied 79 patients with aPL (47 with previous thrombosis), 45 healthy volunteers (normal controls, NC), 12 patients with systemic lupus erythematosus (SLE) without aPL and a thrombosis control group (TCG) without thrombophilia (n = 16). Urinary levels (mean, range) of eicosanoids and isoeicosanoids were significantly increased in 39 patients with aPL compared with 25 NC, 11-DH-TXB(2) 164.0 ng/mmol creatinine (9.5-1162.8) versus 43.4 ng/mmol creatinine (4.2-87.6), P < 0.001; IPF(2alpha)III 56.9 pg/mg creatinine (5.5-388.7) versus 27.0 pg/mg creatinine (4.6-87.6), P = 0.03. Both metabolites were significantly correlated (rho = 0.49, P = 0.014), but none correlated with any clinical manifestation or antibody profile. The aPL group presented increased levels of sPsel, sEsel, sVCAM-1, TAT, F1 + 2 and DD, but any soluble marker correlated with IPF2alphaIII. Urinary 11-DH-TXB(2) correlated with sPsel (rho = 0.39, P = 0.04). Compared with SLE controls, the SLE group with aPL had higher levels of F1 + 2. Plasma levels of F1 + 2 and DD were significantly increased and a trend to higher sPsel was found in aPL patients with thrombosis compared with the TCG. Platelet activation, lipid peroxidation and blood coagulation activation seem to be important in the pathophysiology of antiphospholipid syndrome.