This partially randomised controlled, crossover study sought to investigate the effects of normobaric hypoxia (NH) and hypobaric hypoxia (HH) on cognitive performance, the physiological response at rest and after a 3-min step-test. Twenty healthy participants (10 females and 10 males, 27.6±6.2yrs, 73.6±13.7kg, 175.3±8.9cm) completed a cognitive performance test, followed by the modified Harvard-step protocol, in four environments: normobaric normoxia (NN; PiO2: 146.0±1.5mmHg), NH (PiO2: 100.9±1.3mmHg), HH at the first day of ascent (HH1: PiO2 = 105.6±0.4mmHg) and HH after an overnight stay (HH2: PiO2 = 106.0±0.5mmHg). At rest and/or exercise, SpO2, NIRS, and cardiovascular and perceptual data were collected. The cerebral tissue oxygenation index and the cognitive performance (throughput, accuracy, and reaction time) were not different between the hypoxic conditions (all p>0.05). In NH, SpO2 was higher compared to HH1 (ΔSpO2 NH vs HH1: 1.7±0.5%, p = 0.003) whilst heart rate (ΔHR NH vs HH2: 5.8±2.6 bpm, p = 0.03) and sympathetic activation (ΔSNSi NH vs HH2: 0.8±0.4, p = 0.03) were lower in NH compared to HH2. Heart rate (ΔHR HH1 vs HH2: 6.9±2.6 bpm, p = 0.01) and sympathetic action (ΔSNSi HH1 vs HH2: 0.9±0.4, p = 0.02) were both lower in HH1 compared to HH2. In conclusion, cognitive performance and cerebral oxygenation didn’t differ between the hypoxic conditions. SpO2 was only higher in NH compared to HH1. In HH2, heart rate and sympathetic activation were higher compared to both NH and HH1. These conclusions account for a PiO2 between 100–106 mmHg.