Background: Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a premalignant condition of the oral cavity. Zinc is an essential trace element, necessary for plants, animals, and microorganisms. Hence; the present study was undertaken for assessing serum zinc levels in OSMF patients. Materials & Methods: A total of 40 cases of OSMF and 40 cases of without any lesion and habit (normal control) were included in the present study. The tissue sections were stained with hematoxylin and eosin (H & E) stain to confirm the diagnosis of OSMF. Blood samples were drawn by venipuncture into vacutainer tubes and the samples were immediately centrifuged, after clotting, in patches of five clotted blood samples. The serum obtained was kept in freeze at −20 C until it was analyzed for serum zinc with atomic absorbtion spectrophotometry. Results: Mean Serum zinc levels among the patients of the OSMF group and control group was 56.32 μg/dL and 88.46 μg/dL respectively. Significant results were obtained while comparing the mean serum Zinc levels among patients of the two study groups. Conclusion: Our findings suggest that serum zinc levels could be used as potential prognostic and diagnostic markers in OSMF patients. Key words: Zinc, Oral submucosal fibrosis