Many evidences have correlated neonatal diseases with oxidative stress (OS) caused by the harmful effect of free radicals (FRs). FRs are reactive oxygen and nitrogen species formed as a result of normal cellular metabolism and have many roles in cell signalling pathways. FRs can be also produced in the course of hypoxia, ischemia, ischemia-reperfusion, hyperoxia, inflammation and as consequence of exposition to many endogenous and exogenous oxidising agents. OS injury occurs when tissues, cells and biomolecules undergo an excessive exposition to oxidising agents, both endogenous (substances produced by inflammatory cells) and exogenous (environmental toxins). The FRs production exceeds antioxidant defences and OS occurs. OS is on the basis of several human pathologies such as stroke, hypertension, diabetes, rheumatic diseases, multiple sclerosis, neurodegenerative diseases and cancer. In Neonatology, OS is involved in the development of several FR-related diseases (FRRD) such as oxidative hemolysis, intraventricular haemorrhage, necrotizing enterocolitis, retinopathy of prematurity, chronic lung disease, renal failure. The damaging effect of FRs in perinatal period may be demonstrated by measuring OS biochemical markers in amniotic fluid and in cord blood. Intrauterine hypoxia induces OS in pregnancies with fetal growth restriction (FGR). Prostanoids concentration, actually considered as the best biomarker of OS, are particularly elevated in amniotic fluid of pregnancies with Down syndrome affected fetuses and in cord blood of newborns from maternal chorioamnionitis. They also have a significant predictive value to early detect pregnancies at high risk of premature rupture of membranes, fetuses suffering FGR and newborns who will develop the FRRD.