We have previously demonstrated placentas from laboring deliveries at high altitude have lower binding of hypoxia-inducible transcription factor (HIF) to DNA than those from low altitude. It has recently been reported that labor causes oxidative stress in placentas, likely due to ischemic hypoxic insult. We hypothesized that placentas of high altitude residents acquired resistance, in course of their development, to oxidative stress during labor. Full thickness placental tissue biopsies were collected from laboring vaginal and non-laboring C-section term (37 - 41 wks) deliveries from healthy pregnancies at sea-level and 3100 m. After freezing in liquid nitrogen within 5 minutes of delivery, hydrophilic and lipid metabolites were quantified using ³¹P and ¹H magnetic resonance spectroscopy (MRS) metabolomics. Metabolic markers of oxidative stress, increased glycolysis and free amino acids were present in placentas following labor at sea-level, but not at 3100m. In contrast, at 3100m the equivalent placentas were characterized by the presence of concentrations of stored energy potential (phosphocreatine), anti-oxidants and low free amino acid concentrations. Placentas from pregnancies at sea-level subjected to labor display evidence of oxidative stress. However, equivalent placentas at 3100m have little or no oxidative stress at the time of delivery, suggesting greater resistance to ischemia-reperfusion. We postulate that hypoxic pre-conditioning might occur in placentas that develop at high altitude.