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Background: Studies with single-session hyperbaric oxygen exposures have shown that HBO-induced oxidative stress is proportional to exposure pressure and duration. Since the efficacy of hyperbaric oxygen mainly depends on repetitive exposures, this study aimed to investigate the oxidative effect of hyperbaric oxygen administered for 5 to 40 sessions. Methods: Sixty rats were divided into one control and 6 study groups. Study groups were exposed to 5, 10, 15, 20, 30, and 40 daily consecutive 2.8 atm/90 min hyperbaric oxygen sessions. Animals were sacrificed 24 h after the last hyper­baric oxygen administration. Malondialdehyde and carbonylated protein levels as well as superoxide dismutase activities were determined in isolated rat erythrocytes. Results: Carbonylated protein levels increased significantly after just 5 hyperbaric oxygen exposures; reached a peak level with 10 exposures; were still significantly higher than controls after 15 sessions; and decreased to normal limits after 20 exposures. Malondialdehyde levels were found to be significantly increased in the 10 to 30, but not in the 5 and 40-session groups. Superoxide dismutase activity showed elevated levels only in the 5 and 10 times hyperbarical oxygen- exposed groups. Conclusions: The suppressed oxidative stress level after 40 exposures suggests an effective endogenous antioxidant defense in repetitive HBO administrations.