Repeated sprint in hypoxia (RSH) is used to improve supramaximal cycling capacity, but little is known about the potential differences between different systems for creating normobaric hypoxia, such as a chamber, tent, or mask. This study aimed to compare the environmental (carbon dioxide (CO2) and wet-globe bulb temperature (WGBT)), perceptual (pain, respiratory difficulty, and rate of perceived exertion (RPE)), and external (peak and mean power output) and internal (peak heart rate (HRpeak), muscle oxygen saturation (SmO2), arterial oxygen saturation (SpO2), blood lactate and glucose) workload acute effects of an RSH session when performed inside a tent versus using a mask. Twelve well-trained cyclists (age = 29 ± 9.8 years, VO2max = 70.3 ± 5.9 mL/kg/min) participated in this single-blind, randomized, crossover trial. Participants completed four sessions of three sets of five repetitions × 10 s:20 s (180 s rest between series) of all-out in different conditions: normoxia in a tent (RSNTent) and mask-on (RSNMask), and normobaric hypoxia in a tent (RSHTent) and mask-on (RSHMask). CO2 and WGBT levels increased steadily in all conditions (p < 0.01) and were lower when using a mask (RSNMask and RSHMask) than when inside a tent (RSHTent and RSNTent) (p < 0.01). RSHTent presented lower SpO2 than the other three conditions (p < 0.05), and hypoxic conditions presented lower SpO2 than normoxic ones (p < 0.05). HRpeak, RPE, blood lactate, and blood glucose increased throughout the training, as expected. RSH could lead to acute conditions such as hypoxemia, which may be exacerbated when using a tent to simulate hypoxia compared to a mask-based system.