Résumé : Study Objectives: Exposure to hypoxia elevates chemosensitivity, which can lead to periodic breathing. Exercise impacts gas exchange, altering chemosensitivity; however, interactions between sleep, exercise and chronic hypoxic exposure have not been examined. This study investigated whether exercise exacerbates sleep-related periodic breathing in hypoxia. Methods: Two experimental phases. Short-Term Phase: a laboratory controlled, group-design study in which 16 active, healthy men (age: 25 ± 3 y, height: 1.79 ± 0.06 m, mass: 74 ± 8 kg) were confined to a normobaric hypoxic environment (FIO2 = 0.139 ± 0.003, 4,000 m) for 10 days, after random assignment to a sedentary (control, CON) or cycle-exercise group (EX). Long-Term Phase: conducted at the Concordia Antarctic Research Station (3,800 m equivalent at the Equator) where 14 men (age: 36 ± 9 y, height: 1.77 ± 0.09 m, mass: 75 ± 10 kg) lived for 12-14 months, continuously confined. Participants were stratified post hoc based on self-reported physical activity levels. We quantified apnea-hypopnea index (AHI) and physical activity variables. Results: Short-Term Phase: mean AHI scores were significantly elevated in the EX group compared to CON (Night1 = CON: 39 ± 51, EX: 91 ± 59; Night10 = CON: 32 ± 32, EX: 92 ± 48; P = 0.046). Long-Term Phase: AHI was correlated to mean exercise time (R2 = 0.4857; P = 0.008) and the coefficient of variation in night oxyhemoglobin saturation (SpO2; R2 = 0.3062; P = 0.049). Conclusions: Data indicate that exercise (physical activity) per se affects night SpO2 concentrations and AHI after a minimum of two bouts of moderateintensity hypoxic exercise, while habitual physical activity in hypobaric hypoxic confinement affects breathing during sleep, up to 13+ months' duration.