Ramos-Campo, DJ, Rubio-Arias, JÁ, Freitas, TT, Camacho, A, Jiménez-Diaz, JF, and Alcaraz, PE. Acute physiological and performance responses to high-intensity resistance circuit training in hypoxic and normoxic conditions. J Strength Cond Res 31(4): 1040–1047, 2017—The aim of this study was to analyze physical performance and physiological variables during high-intensity resistance circuit training (HRC) with the addition of 2 levels (moderate and high) of systemic hypoxia. Twelve resistance-trained young male subjects participated in the study. After a 6 repetition maximum testing session, participants performed 3 randomized trials of HRC: normoxia (NORM: fraction of inspired oxygen [FiO2] = 0.21; ∼0 m altitude), moderate hypoxia (MH: FiO2 = 0.16; ∼2.100 m altitude), or high hypoxia (HH: FiO2 = 0.13; ∼3.800 m altitude), as controlled by a hypoxic generator. Bench press force, heart rate and heart rate variability, rating of perceived exertion, resting metabolic rate, energy cost, and countermovement jump were assessed in each session. Heart rate variability in HH was significantly lower (standard deviation of all normal NN intervals [intervals between two “normal” beats] = 111.9 vs. 86.7 milliseconds; standard deviation of the difference between consecutive NN intervals = 19.5 vs. 17.0 milliseconds; p ≤ 0.05) in comparison with NORM. There were significant differences in rating of perceived exertion between NORM and HH (11.6 vs. 13.8 points). Peak and mean force on the bench press were significantly lower (p ≤ 0.05) in HH when compared with MH (peak: 725 vs. 488 N; mean: 574 vs. 373 N). Energy cost was significantly higher (p ≤ 0.01) in both hypoxic conditions compared with NORM (NORM: 10.4; MH: 11.7; HH: 13.3 kJ·min−1). There were no differences between conditions in heart rate and countermovement jump variables. These results indicate that hypoxic stimuli during HRC exercise alter physical performance and physiological variables and affect how strenuous the exercise is perceived to be. High-intensity resistance circuit training in hypoxia increases the stress on the performance and physiological responses, and these differences must be taken into account to avoid an excessive overload.