Abstract The purpose of this study was to examine the effects of acute normobaric (NH, decreased FiO 2 ) and hypobaric (HH, 4200 m ascent) hypoxia exposures compared to sea level (normobaric normoxia, NN). Tissue oxygenation, cardiovascular, and body fluid variables measured during rest and a 3-min step-test following 90-min exposures (NH, HH, NN). Muscle oxygenated hemoglobin (O 2 Hb) decreased, and muscle deoxygenated hemoglobin (HHb) increased environmentally independent from rest to exercise ( p textless 0.001). During exercise, brain O 2 Hb was lower at HH compared to NN ( p = 0.007), trending similarly with NH ( p = 0.066), but no difference between NN and NH ( p = 0.158). During exercise, HR at NH (141 ± 4 beats·min −1 ) and HH (141 ± 3 beats·min −1 ) were higher than NN (127 ± 44 beats·min −1 , p = 0.002), but not each other ( p = 0.208). During exercise, stroke volume at HH (109.6 ± 4.1 mL·beat −1 ) was higher than NH (97.8 ± 3.3 mL·beat −1 ) and NN (99.8 ± 3.9 mL·beat −1 , p ≤ 0.010) with no difference between NH and NN ( p = 0.481). During exercise, cardiac output at NH (13.8 ± 0.6 L) and HH (15.5 ± 0.7 L) were higher than NN (12.6 ± 0.5 L, p ≤ 0.006) with HH also higher than NH ( p = 0.001). During acute hypoxic stimuli, skeletal muscle maintains oxygenation whereas the brain does not. These differences may be mediated by environmentally specific cardiovascular compensation. Thus, caution is advised when equating NH and HH.