Abstract: Background and Objective: Sepsis is a condition that causes multiple organ failure leading to mortality. Oxidative stress has a pivotal role in the development of sepsis causing organ failure. So, the aim of this study was to analyze the effect of vanillic acid on sepsis-induced liver damage in rats. Materials and Methods: Male Sprague Dawley rats were segregated into four groups; sham group, sepsis control group, vanillic acid control group and vanillic acid treated sepsis group. Sepsis was induced by cecal ligation and puncture (CLP). Rats were intraperitoneally (i.p.) injected with 100 mg kg–1 b.wt. vanillic acid in 0.5 mL kg–1 b.wt. saline upon sepsis induction and sacrificed after 24 h of treatment for biochemical and histopathological analysis. Results: The levels of reduced glutathione (GSH) and antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase) were markedly reduced (p<0.05) in the sepsis control group. Malondialdehyde (MDA) levels, liver damage markers (AST, ALT, ALP) and pro-inflammatory cytokines (TNF-α, IL-6) in the liver tissues and plasma of rats were elevated (p<0.05) in sepsis control group. Treatment with vanillic acid significantly reversed (p<0.05) the effects of sepsis on oxidative stress markers and pro-inflammatory cytokine levels compared to sepsis control group. Histopathological changes in liver were observed in vanillic acid treated rats as compared to sepsis control group. Conclusion: So, it was concluded that vanillic acid is able to prevent the progression of sepsis and protect against oxidative liver injury. Further research is needed to ascertain the mechanism of vanillic acid in preventing sepsis-induced organ damage.