Future space missions are expected to include increased extravehicular activities (EVAs) during which astronauts are exposed to high-energy space radiation while breathing 100% oxygen. Given that brain irradiation can lead to cognitive impairment, and that oxygen is a potent radiosensitizer, there is a concern that astronauts may be at greater risk of developing cognitive impairment when exposed to space radiation while breathing 100% O₂ during an EVA. To address this concern, unanesthetized, unrestrained, young adult male Fischer 344 × Brown Norway rats were allowed to breathe 100% O₂ for 30 min prior to, during and 2 h after whole-body irradiation with 0, 1, 3, 5 or 7 Gy doses of 18 MV X rays delivered from a medical linear accelerator at a dose rate of ~425 mGy/min. Irradiated and unirradiated rats breathing air (~21% O₂) served as controls. Cognitive function was assessed 9 months postirradiation using the perirhinal cortex-dependent novel object recognition task. Cognitive function was not impaired until the rats breathing either air or 100% O₂ received a whole-body dose of 7 Gy. However, at all doses, cognitive function of the irradiated rats breathing 100% O₂ was improved over that of the irradiated rats breathing air. These data suggest that astronauts are not at greater risk of developing cognitive impairment when exposed to space radiation while breathing 100% O₂ during an EVA.