Warfighters engaging in combat are susceptible to traumatic injuries that may require hemorrhage control at the point of injury (POI). Recent evidence suggests that use of fresh whole blood transfusion (FWBT) as a battlefield expedient resuscitation method improves warfighter survivability. To perform FWBT at POI, a donor must be hematologically compatible and available to donate up to 500 ml of blood. Following donation, a warfighter may have to quickly return to the battlefield. However, potential performance decrements of the donor in military, operationally relevant environments are unknown. PURPOSE: Determine the influence of blood donation on exercise performance and physiological perception at high-altitude in near freezing temperatures. METHODS: Fourteen military personnel (mean ± SD age: 28 ± 6 yrs; ht: 175 ± 7 cm; wt: 78.4 ± 9.1 kg) completed a two-day FWBT training in a mountainous environment (2,800 m). Each day, participants hiked (3.2 km out-and-back; 250 m elevation gain) in the snow with loaded rucksacks (mean ± SD: 24.2 ± 2.1 kg) with (FWBT) or without (CON) providing a 500 ml blood donation. Heart rate (HR), core temperature (Tc), oxygen saturation (SpO2), respiratory rate (RR), minute ventilation (VE), and oxygen consumption (VO2) were measured. Ratings of perceived exertion (RPE), thermal sensation (TS), and acute mountain sickness were obtained five times throughout each hike. Repeated measures ANOVAs were performed to compare responses to exercise between FWBT and CON. RESULTS: Although exercise at altitude influenced nearly all measurements, no differences between CON and FWBT were observed for hiking time (CON: 56 ± 15 min; FWBT: 57 ± 15 min; p = 0.864), HR (CON: 144 ± 18 bpm; FWBT: 146 ± 14 bpm; p = 0.584), Tc (CON: 38.0 ± 0.5 °C; FWBT: 38.0 ± 0.4 °C; p = 0.716), RPE (CON: 3.9 ± 1.5; FWBT: 4.3 ± 1.2; p = 0.100), TS (CON: 1.0 ± 0.8; FWBT: 1.2 ± 1.1; p = 0.457), Fatigue (CON: 0.3 ± 0.4; FWBT: 0.5 ± 0.6; p = 0.090), and dizzy/lightheaded (CON: 0.0 ± 0.1; FWBT: 0.1 ± 0.3; p = 0.255), among others. CONCLUSIONS: Findings suggest that blood donation at high-altitude does not impair exercise and associated physiological perceptions. These results inform commander, medical provider, and warfighter understanding of potential limitations and consequences of POI resuscitation and prolonged field care in austere environments.