Objectives: Twins represent a unique natural model for studying fetal adaptation to a suboptimal supply of nutrients in utero, the most likely cause of reduced fetal growth, which has been associated with cardiovascular risk. The proposed developmental origin of cardiovascular diseases may offer new venues for investigating the molecular basis of the well-known gender disparity in cardiovascular disease pathogenesis and progression. Early sex differences in oxidative stress, a mechanism of injury associated with both reduced fetal growth and cardiovascular diseases, have been so far poorly investigated. Thus, we aimed at evaluating oxidative stress in newborn twins by measuring oxidative stress biomarkers in cord blood. Methods: Blood samples were collected from umbilical cord of 80 premature twins. The oxidative stress biomarker15-F_2t-isoprostane and the total antioxidant capacity (tAOC) were measured in cord plasma. Results: Males had higher levels of plasma 15-F_2t-isoprostane than females. 15-F_2t-isoprostane values remained greater in males than in females when considering like-sex or unlike sex pairs. No difference was found in tAOC levels. Conclusions: Our data suggest that sex-based differences in oxidant injury vulnerability occurring early in life could represent a biological mechanism contributing to gender disparity later in life.