Background: The present study evaluated serum antioxidant enzymes in oral submucous fibrosis and oral squamous cell carcinoma. Materials & Methods: 30 cases of OSMF and 25 cases of OSCC of both genders. 30 healthy subjects were also enrolled. 6 ml of blood samples were collected with a tourniquet applied 1½-2 inch above the antecubital fossa. The collected blood was centrifuged and the plasma separated was analyzed for vitamin E, beta carotene, MDA. Results: The mean vitamin E level was 7.19 in group I, 6.52 in group II and 9.12 in group III. Beta carotene level was 70.3 in group I, 62.3 in group II and 114.5 in group III. MDA level was 9.16 in group I, 13.4 in group II and 2.91 in group III. The difference was significant (P< 0.05). Conclusion: There was increased level of MDA and decreased level of vitamin E and beta carotene.in OSMF and OSCC patients.