Present study was undertaken to estimate and compare erythrocyte superoxide dismutase (E-SOD) and Glutathione peroxidase (GPx) levels in oral submucous fibrosis, oral leukoplakia and oral cancer patients and age/sex matched healthy subjects, 25 in each group. Statistically significant (P<0.001) decrease in E-SOD and GPx levels were observed in OSF, oral leukoplakia and oral cancer groups as compared to the control group. Oral leukoplakia group showed lower levels in comparison with OSF (P>0.05). Oral cancer group had the lowest levels amongst the study groups. Imbalance in antioxidant enzyme status may be considered as one of the factors responsible for the pathogenesis of cancer and may serve as a potential biomarker and therapeutic target to reduce the malignant transformation in oral premalignant lesions/conditions.