Hyperoxia results from the inhalation of mixtures of gas containing higher partial pressures of oxygen (O2) than normal air at sea level. Exercise in hyperoxia affects the cardiorespiratory, neural and hormonal systems, as well as energy metabolism in humans. In contrast to short-term exposure to hypoxia (i.e. a reduced partial pressure of oxygen), acute hyperoxia may enhance endurance and sprint interval performance by accelerating recovery processes. This narrative literature review, covering 89 studies published between 1975 and 2016, identifies the acute ergogenic effects and health concerns associated with hyperoxia during exercise; however, long-term adaptation to hyperoxia and exercise remain inconclusive. The complexity of the biological responses to hyperoxia, as well as the variations in (1) experimental designs (e.g. exercise intensity and modality, level of oxygen, number of participants), (2) muscles involved (arms and legs) and (3) training status of the participants may account for the discrepancies.