Abstract: Purpose: The aim of our study was to evaluate the efficacy and timing of hyperbaric oxygen (HBO) treatment in sepsis. Materials and methods: Forty male adult Wistar rats were divided into five groups: in group 1, 1 ml of 0.9% saline solution was injected intraperitoneally; in group 5, 1 ml of 0.5 Mc Farland E. coli solution was injected intraperitoneally; in groups 2, 3 and 4, 1 ml of 0.5 Mc Farland E. coli solutions were injected intraperitoneally and the rats were treated with HBO at 2.5 ATA with 6 hour intervals after the 2nd, 6th and 12th hours of injection, respectively. At the end of the treatment, tissue levels of glutathione peroxidase (GP), superoxide dismutase (SOD), catalase (CAT) and lipid hydroperoxide (LPO) from liver, kidney and brain were studied. Results: Mean GP levels of groups 2, 3 and 4 were higher than group 5 (all p values being <0.05). Mean GP level of group 2 was higher than those of groups 3 and 4 (p values <0.05) which were statistically indifferent. Mean kidney and liver CAT levels in groups 2, 3 and 4 were higher than group 5. Mean CAT level of group 2 was statistically higher when compared with those of groups 3 and 4 (p values <0.05). Brain and kidney LPO levels of groups 2 and 3 were lower than groups 4 and 5 (p values <0.05). Liver LPO levels of group 2 were lower than those of groups 3 and 4 (p<0.05). Conclusions: Overall, we imply that HBO treatment can be an adjunct to other well established treatment modalities and it seems likely that the early it is started the better will be the outcome. Further studies with larger samples are needed to confirm our preliminary results.