Background: We tested the hypothesis that controlled hypoxemic resuscitation of hypoxic newborn piglets improves early cerebral metabolic and electrophysiological recovery. Subjects: Twenty-four 2-5 days old piglets. Interventions: Hypoxia was induced by ventilating the piglets with 6% O2 in N2. When EEG became isoelectric, and either mean arterial blood pressure fell below 25 mm Hg or base excess (BE) was lower than -25 mmol/L, a 2 h resuscitation period was started. The piglets were randomly divided into three resuscitation groups: Hypoxemic (n=8), 21% O2 (n=8), and 100% O2 group (n=8). The hypoxemic group was ventilated with 12-18% O2 to achieve a cerebral venous oxygen saturation of 17-23% (baseline; 44±6%). Results: BE reached-22±6 mmol/L (mean±SE) at the end of hypoxia. PaO2 at 30 min of resuscitation were 6.0±0.4, 9.9±0.5, and 57.5±2.7 kPa in the hypoxemic, 21% O2, and 100% O2 group. No significant differences in time to recovery of EEG (p=0.17), quality of EEG at recovery (p=0.22), or extracellular hypoxanthine concentrations in cerebral cortex and striatum were found between the groups. Brain cell membrane Na+,K+-ATPase activity at the end of resuscitation was not different between the groups (p=0.30). BE and plasma hypoxanthine, however, normalized during hypoxemic resuscitation significantly slower than during resuscitation with 21% or 100% O2.Conclusion: Controlled hypoxemic resuscitation did not improve early brain recovery compared with resuscitation with 21% and 100% O2, and showed a delayed metabolic correction of the total body hypoxia. In contrast, resuscitation with 21% O2 was as efficient as resuscitation with 100% O2 in this newborn piglet hypoxia model.