We tested the hypothesis that hypoxic newborn piglets can be successfully resuscitated with lower O2 concentrations than 21%. Methods: Hypoxia was induced in 45 anesthetized and instrumented newborn piglets by ventilating them with 8% O2 in N2. When SEP was abolished and mean arterial blood pressure fell below 20 mm Hg, a 3 hour resuscitation period was started. The piglets were randomly divided into five groups: 21% O2 (n=10), 18% O2 (n=9), 15% O2 (n=9), 12% O2(n=8), all normoventilated (PaCO2 = 34 to 45 mm Hg) and a hypoventilated 21% O2 group (PaCO2 = 52 to 60 mm Hg, n=9). Results: Arterial oxygen tensions at 30 min of resuscitation were(mean ± SEM) 84±2, 67±3, 46±2, 42±2, and 62±3 mm Hg in the 21%, 18%, 15%, 12%, and hypoventilated groups, respectively. Mean base excess (BE) was -19 to -22 mmol/L at the end of hypoxia (p=0.90 between all groups). After 3 hours BE had risen to-4 ± 1 mmol/L both in the 21%, 18%, and the hypoventilated groups, but was -10±2 (p<0.05 vs. 21% O2 group) and-22±2 mmol/L (p<0.05 vs. 21% O2 group) in the 15% and 12% O2 groups. SEP recovered in 39 of 45 animals during resuscitation (p=0.61 between all groups), and remained present during resuscitation in all groups except the 12% O2 group. SEP recovered even in 6 of 8 animals in the 12% O2 group, but disappeared in all later during resuscitation, and four of these 8 animals died. The SEP amplitude at the end of resuscitation was 63±17, 62±17, 67±12, and 47±15% of baseline in the 21%, 18%, 15%, and hypoventilated groups, respectively (p=0.71). The SEP latency did not show any differences between the groups. Conclusion: Resuscitation with 18% O2 and hypoventilation with 21% O2 normalizes both the metabolic acidosis and SEP as efficiently as resuscitation with 21% O2. Resuscitation with 15% O2, however, normalizes SEP, but not the metabolic acidosis as efficiently as 21% O2.