Strickland, Brian, Elan Small, Mary Ryan, and Ryan Paterson. Effectiveness of continuous positive airway pressure in alleviating hypoxemia and improving exertional capacity at altitude. High Alt Med Biol. 00:000-000, 2024. Introduction: Decreased oxygen saturation and exercise tolerance are commonly experienced at high altitude. Continuous positive airway pressure (CPAP) devices have become increasingly portable and battery powered, providing a potentially unique new therapeutic modality for treatment of altitude-related illnesses. This study evaluated the potential use of CPAP devices to improve and maintain oxygen saturation at altitude, both at rest and with exertion, to evaluate the feasibility of using this device at altitude. Methods: Subjects were taken to Mount Blue Sky and monitored while they hiked to the summit (4,350 m), maintaining a consistent level of exertion. Subjects hiked for 0.7 km both with and without CPAP set to 10 cmH2O pressure. Continuous vital signs were collected during the hike and recovery period. Results: All subjects completed the hike wearing CPAP devices at a vigorous level of exertion. Mean oxygen saturation of the CPAP group (M = 83.8%, SD = 3.72) was significantly higher than that of the control group during exertion (M = 78.7%, SD = 2.97); p = 0.005. Recovery after exertion was quicker in the CPAP group than the control group. Three subjects experienced claustrophobia requiring a brief pause, but were able to complete their exercise trial without removing equipment or experiencing adverse events. When pauses from claustrophobia were excluded, there was no difference in completion time between the groups (p = 0.06). Conclusion: CPAP reliably improved oxygen saturation at rest and during vigorous exertion at high altitude. Its ability to correct hypoxemia, even with physical exertion, may prove useful after further study as a portable self-carried device to prevent and treat altitude-related illness, or to improve safety in high-altitude rescues.