Hyperoxia is both an essential therapy and a contributor to lung injury in acute respiratory distress syndrome. We hypothesized that adult female rats are relatively protected from hyperoxia-induced acute lung injury (HALI) compared with males and that this protection is associated with sex-dependent differences in lung mitochondrial bioenergetics and H 2 O 2 production. Adult rats were exposed to room air (normoxia) or hyperoxia (>95% O 2 ) for up to 60 h. Lung injury was assessed by pleural ef