Our aim was to investigate the activities of antioxidative defense enzymes in the placenta, fetal blood and amnion fluid in inherited thrombophilia. Thrombophilia was associated with nearly threefold increase of activity (p < 0.001) of the placental catalase (81.1 ± 20.6 U/mg of proteins in controls and 270.0 ± 69.9 U/mg in thrombophilic subjects), glutathione (GSH) peroxidase (C: 20.2 ± 10.1 U/mg; T: 60.0 ± 15.5 U/mg), and GSH reductase (C: 28.9 ± 5.6 U/mg; T: 72.7 ± 23.0 U/mg). The placental activities of superoxide dismutating enzymes—MnSOD and CuZnSOD, did not differ in controls and thrombophilia. Likewise, the activities of catalase and SOD in the fetal blood, and the level of ascorbyl radical which represents a marker of oxidative status of amniotic fluid, were similar in controls and thrombophilic subjects. From this we concluded that in thrombophilia, placental tissue is exposed to H2O2-mediated oxidative stress, which could be initiated by pro-thrombic conditions in maternal blood. Increased activity of placental H2O2-removing enzymes protects fetus and mother during pregnancy, but may increase the risk of postpartum thrombosis.