Purpose The combined effects of acute hypoxia and exercise on cognition remain to be clarified. We investigated the effect of speed climbing to high altitude on reactivity and inhibitory control in elite climbers. Methods Eleven elite climbers performed a speed ascent of the Mont-Blanc (4810 m) and were evaluated pre-(at 1000 m) and immediately post-ascent (at 3835 m). In both conditions, a Simon task was done at rest (single-task session, ST) and during a low-intensity exercise (dual-task session, DT). Prefrontal cortex (PFC) oxygenation and middle cerebral artery velocity (MCAv) were monitored using near-infrared spectroscopy and transcranial Doppler, respectively, during the cognitive task. Self-perceived mental fatigue and difficulty to perform the cognitive tests were estimated using a visual analog scale. Heart rate and pulse oxygenation (SpO 2) were monitored during the speed ascent. Results Elite climbers performed an intense (~ 50% of the time ≥ 80% of maximal heart rate) and prolonged (8h58 ± 6 min) exercise in hypoxia (minimal SpO 2 at 4810 m: 78 ± 4%). Reaction time and accuracy during the Simon task were similar pre-and post-ascent (374 ± 28 ms vs. 385 ± 39 ms and 6 ± 4% vs. 5 ± 4%, respectively; p > 0.05), despite a reported higher mental fatigue and difficulty to perform the Simon task post-ascent (all p < 0.05). The magnitude of the Simon effect was unaltered (p > 0.05), suggesting a preserved cognitive control post-ascent. Pattern of PFC oxygenation and MCAv differed between pre-and post-ascent as well as between ST and DT conditions. Conclusions Cognitive control is not altered in elite climbers after a speed ascent to high-altitude despite substantial cerebral deoxygenation and fatigue perception.