BACKGROUND: Hemorrhage and traumatic brain injury can be lethal if left unattended. The transportation of severely wounded combat casualties from the battlefield to higher level of care via aeromedical evacuation (AE) may result in unintended complications. This could become a serious concern at the time of evacuation of mass casualties or for prolonged field care scenarios with limited resources. METHODS: Following instrumentation (t1), anesthetized Sprague-Dawley rats were injured or not [75-kPa blast and 30% estimated blood-volume controlled hemorrhage] (t2). After 15 min, all rats were resuscitated with saline. During the simulated 3-h evacuation, 8000 ft (2440 m) vs. sea-level heart rate, temperature, and oxygenation (Spo2) were continuously recorded. One group of rats was euthanized immediately after evacuation (t3) and another after a 72-h recovery period (t4). Hematology and metabolic levels were measured at t1, t2, t3, and t4. RESULTS: Survival was 100% in control-uninjured animals, 83% in injured animals under normobaria, and significantly reduced to 50% under hypobaria. This AE setting resulted in significantly lower hemodynamics, thermoregulation, and oxygenation parameters in the animals under hypobaria than those under normobaria. The initial lower mean arterial pressure (MAP) with the reduced oxygen level before AE were critical factors for the survival of injured animals. We observed a general increase of white blood cells and platelet ability to aggregate at t4 in all experimental groups. CONCLUSION: Physiological parameters were affected during aeromedical evacuation in all groups. This was worsened for injured animals with MAP less than 60 mmHg associated with low Spo2 in a simulated aeromedical evacuation. This represented a high risk of mortality for severely polytraumatized animals.