Sepsis, often initiated by an infection, is a state of disrupted inflammatory homeostasis. There is increasing evidence that oxidative stress has an important role in the development of sepsis-induced multiorgan failure. Resveratrol (RV) is a polyphenolic compound found in the skin of red fruits, such as mulberries and red grapes, and in peanuts. RV has been reported to have an antioxidant, antiproliferative, and anti-inflammatory properties in various models. It has also been found to inhibit the proliferation of a variety of human cancer cell lines, including breast, prostate, colon, pancreatic, and thyroid. This study has been undertaken to assess the role of RV on the sepsis-induced oxidative DNA damage in the lymphocytes of Wistar albino rats by the standard and formamidopyrimidine DNA glycosylase (Fpg)-modified comet assays. The parameters of tail length, tail intensity, and tail moment were evaluated for the determination of DNA damage. According to the study, the DNA damage was found to be significantly higher in the sepsis-induced rats when compared with the control rats (p < 0.05). The parameters were significantly decreased in the RV-treated sepsis-induced group when compared with the sepsis-induced group. The parameters in the sepsis-induced rats were found to be significantly higher in the Fpg-modified comet assay when compared with the standard comet assay (p < 0.05), and RV treatment decreases the DNA damage in the sepsis-induced rats, suggesting that the oxidative stress is likely to be responsible for DNA damage and RV might have a role in the prevention of sepsis-induced oxidative DNA damage.