Objectives: Natural medicine has been proposed in treating of sepsis in the worldwide. So, in this study, the effect of deuterium-depleted water (DDW) alone and adjuvant with Rosa damascene Mill. essential oils (RD) was considered through the evaluation of oxidative stress/antioxidant parameters and the expression of cyclooxygenase-2 (COX-2) inflammatory gene in liver damage caused by sepsis. Materials and Methods: The rats were randomly divided into 5 groups: 1) laparotomy (LAP) group; 2) cecal ligation and puncture (CLP) group; 3) DDWs (15ppm and 30 ppm doses) groups; 4) DDWs (15ppm and 30 ppm doses) plus RD (100mg/kg.bw); 5) indomethacin (2 mg/kg.bw) as a positive control. The treatments were daily done for two weeks and creation of CLP model was occurred on the 15 th day. Then, the animals were killed and their liver tissue were separated for histopathologic and biochemical assessments. Results: Our results demonstrated that the treatment of animals with DDWs and DDWs plus RD were effective due to regulating the oxidative stress/antioxidant parameters including lipid peroxidation (LP), glutathione (GSH), glutathione s-transferases (GST), myeloperoxidase (MPO), ferric reducing ability of plasma (FRAP) and inflammatory parameters such as prostaglandin E2 (PGE2) and COX-2. Pathological studies also showed that sepsis led to the liver tissue injuries, which can be reduced by treatments. u n c o r r e c t e d p r o o f 2 Conclusion: Sepsis caused oxidative stress resulting in the liver tissue, but the administration of DDWs and DDWs plus RD can be useful to prevent and improve these injuries.