Perinatal asphyxia is one of the leading causes of morbidity and mortality in the neonatal period. Response to oxygen treatment is unpredictable and the optimum concentration of oxygen in neonatal resuscitation is still a matter of debate among neonatologists. A metabolomic approach was used to characterize the metabolic profiles of newborn hypoxic-reoxygenated piglets. Urine samples were collected from newborn piglets (n = 40) undergoing hypoxia followed by resuscitation at different oxygen concentrations (ranging from 18% to 100%) and analyzed by ¹H NMR spectroscopy. Despite reoxygenation 7 piglets, out of 10 which became asystolic, did not respond to resuscitation. Profiles of the ¹H NMR spectra were submitted to unsupervised (principal component analysis) and supervised (partial least squares-discriminant analysis) multivariate analysis. The supervised analyses showed differences in the metabolic profile of the urine collected before the induction of hypoxia between survivors and deaths. Metabolic variations were observed in the urine of piglets treated with different oxygen concentrations comparing T0 (basal value) and end of the experiment (resuscitation). Some of the individual metabolites discriminating between these groups were urea, creatinine, malonate, methylguanidine, hydroxyisobutyric acid. The metabolomic approach appears a promising tool for investigating newborn hypoxia over time, for monitoring the response to the treatment with different oxygen concentrations, and might lead to a tailored management of the disorder.