Aims and Objectives: The aim of the study was to study serum lipid profile and compare their levels in patients with oral sub mucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC). Materials and Methods: This study was done in two groups of patients ‑ OSMF and OSCC. There were forty five participants in each group. Serum obtained from centrifugation of 12 hour fasting blood samples was analyzed on fully automated analyzer Beckman coulter AU680 for estimating the lipid levels (cholesterol, triglycerides [TGL], and high‑density lipids [HDL]) by colorimetric method. Low‑density lipid [LDL] values were obtained by calculator. Results: The comparison of lipid profile between Oral Submucous Fibrosis and Oral Carcinoma cases shows statistically significant results for TC, HDL and LDL. Conclusion: The change in lipid levels may have an early diagnostic or prognostic role in oral premalignant and malignant lesions.