We evaluated the cognitive effects of hypoxemia independent of hypocapnia in 20 right-handed male subjects using a battery of brief neuropsychological tests. Results of a profile analysis indicated that performance during hypoxia was reliably different for Digit Symbol and Finger Tapping tests. Trend analysis demonstrated a significant linear pattern for Finger Tapping results, such that lower levels of oxygen were associated with slower rates of tapping. No significant trends were observed for Digit Symbol results. The observation of hypoxic effects on Digit Symbol and Finger Tapping tests is consistent with previous findings of neuropsychological changes secondary to hypoxia. The negative results observed for the remaining tests are inconsistent with past literature. It is likely that methodological differences contributed to these discrepancies, including previous reliance on inspired air to index hypoxemia rather than monitoring arterial oxygen saturation directly and failure to control for differences in CO2 levels during induced hypoxia. These variables should be controlled in future research.