Objective: To describe the effect of reoxygenation with 100% O2 as compared to the effect of room air in newborn rat brains after asphyxia. Methods: Experimental asphyxia (carotid artery ligation followed by hypoxic exposure with 8% O2 for 2 h) was performed on 7-day-old rats. After hypoxia-ischemia the rats were reoxygenated with either 100% O2 (hyperoxia group) or 21% O2 (room air group) for 24 h and then returned to the dam. The rats were killed 1 week after the experiment to study the cerebral cortex and hippocampus. Results: Rats reoxygenated with 100% O 2 post-asphyxia showed more frequency of cortical damage (10 of 24 rats) than those reoxygenated with room air (3 of 24 rats) (χ2 test, p = 0.02). Conclusion: We consider that hyperoxia with 100% oxygen after hypoxia-ischemia can cause more damage in the cerebral cortex than room air in newborn rats. Copyright © 2005 S. Karger AG.