Existing evidence indicates that hypoxic conditions compromise cognitive function. It is also known that poikilocapnic hypoxia affects cognitive function to a greater extent than isocapnic hypoxia does. Given the important role that carbon dioxide plays in the regulation of blood flow in the cerebral circulation, it is likely that the impairment in cognitive function is caused, at least in part, by hypocapnia-induced vasoconstriction. However, the link between cerebral blood flow (CBF) alterations and cognitive function in hypoxia has not been clearly defined. The aim of the present study was to determine the effect of hypoxic-induced hypocapnia and its subsequent effect on CBF against changes in cognitive function during a hypoxic challenge.Nine young and healthy participants (5 males, 4 females) undertook two protocols on separate days, in a random order. The protocols consisted of exposure to hypoxia (PETO2 = 45 mm Hg) in either poikilocapnia (PICO2 = 0 mmHg) or isocapnia (PETCO2 = 1 mmHg above each participant’s normal value). Each protocol was preceded by a ~10-minute period in isocapnic euoxia (PETO2 = 100 mmHg and PETCO2 = 1 mmHg above each participant’s normal value) during which baseline cognitive function was assessed. These tests were then repeated under the hypoxic conditions following 60 minutes of exposure. Cognitive function tests involved simple and 5-choice response time tasks (measuring reaction time (RT) and movement time (time to reach the target (MT)) and a spatial working memory task (SWM). Blood flow velocity in the middle cerebral artery (MCAv) was measured throughout. Data are means ± S.E.M.Poikilocapnic hypoxia significantly increased both simple and 5-choice RT and MT (e.g., 5-choice RT: 316.7±16.2 vs. 372.3±15.2 ms (baseline), p<0.01; 5-choice MT: 284.7±13.3 vs. 338.8±24.3 ms (baseline), p=0.02). Isocapnic hypoxia did not have a significant effect on these variables (e.g., 5-choice RT: 311.7±14.3 vs. 313.1±14.1 ms (baseline), p=0.67; 5-choice MT: 288.7±12.1 vs. 290.2±20.1 ms (baseline), p=0.90). These differential effects were confirmed via a significant condition x time interaction for each variable (p≤0.01). The number of errors made in the SWM task was significantly greater in poikilocapnic hypoxia compared to isocapnic hypoxia (3.3±0.9 vs. 11.8±1.3, p<0.01), although the condition x time interaction was not significant (p=0.18). During poikilocapnic hypoxia, MCAv was significantly lower than in isocapnic hypoxia (71.9±4.3 vs. 77.8±3.8 cm/s, p=0.04).Our results confirm that cognitive impairment associated with hypoxia is linked to hypocapnia. The maintenance of cognitive function in isocapnic hypoxia compared to poikilocapnic hypoxia coincides with elevated cerebral perfusion, indicating that hypocapnic-induced reductions in CBF may be a key element in the impairment of cognition during hypoxia.