The effect of altitude on exercise performance of lowlanders has long been discussed, but it is still unclear whether the performance reduction is related to inefficiency of the respiratory system, body tissues or both. In the present work, exergy analysis was applied to the human body in order to compare its exergy efficiency under basal conditions and during physical activity at sea level and high altitudes for different periods of acclimatization. Two control volumes were analyzed: respiratory system and human body as a whole. Data concerning mass and energy balances of the body and respiratory system were obtained from models available in the literature, which were modified based on medical literature to simulate the responses to physical activity at high altitude for different periods of acclimatization. The results indicated that the respiratory system exergy efficiency is reduced at high altitudes and under physical activity, while exergy efficiency of the body increases for both parameters, which may indicate that the discomfort reported at high altitudes is mostly related to the respiratory system than to the other ones. Concerning the acclimatization period, its influence was more pronounced on the respiratory system Ver menos