Background and Objectives: Limited research has evaluated the effects of acute exercise on cognition under different conditions of inspired oxygenation. Thus, the purpose of this study was to examine the effects of high-intensity interval exercise (HIE) under normoxia (inspired fraction of oxygen (FIO ): 0.209) and moderate hypoxia (FIO : 0.154) on cognitive function. Design: A single-blinded cross-over design was used to observe the main effects of exercise and oxygen level, and interaction effects on cognitive task performance. Methods: Twenty inactive adults (10 males and 10 females, 19–27 years old) performed a cognitive task (i.e., the Go/No-Go task) before and immediately after an acute bout of HIE under normoxic and hypoxic conditions. The HIE comprised 10 repetitions of 6 s high-intensity cycling against 7.5% body weight interspersed with 30 s passive recovery. Heart rate, peripheral oxygen saturation (SpO ) and rating of perceived exertion were monitored. Results: The acute bout of HIE did not affect the reaction time (p = 0.204, η = 0.083) but the accuracy rate decreased significantly after HIE under both normoxic and hypoxic conditions (p = 0.001, η = 0.467). Moreover, moderate hypoxia had no influence either on reaction time (p = 0.782, η = 0.004) or response accuracy (p = 0.972, η < 0.001). Conclusions: These results indicate that an acute session of HIE may impair response accuracy immediately post-HIE, without sacrificing reaction time. Meanwhile moderate hypoxia was found to have no adverse effect on cognitive function in inactive young adults, at least in the present study.