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Background: Oral Sub Mucous Fibrosis (OSMF) is a chronic, debilitating disease characterised by juxtaepithelial fibrosis of the oral cavity. It is a precancerous conditiona generalized pathological state of the oral mucosa associated with a significantly increased risk of oral cancer. Lipids are major cell membrane components. The changes in serum lipid levels have long been associated with cancerous and precancerous conditions. So this study is aimed to evaluate the plasma lipid profile in OSMF patients. Objectives. The present study aimed to evaluate the alteration in serum lipid profile in OSMF and to compare them with healthy controls and to correlate the relationship between pathogenesis of OSMF and lipid profile. Materials and methods: It is a case control study. The study included 100 diagnosed cases of OSMF and 100 matched healthy controls. Fasting venous blood of 3 ml was collected in both cases and controls and serum was separated. Fasting serum lipid profile including Total Cholesterol (TC), Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) and Tri-Glycerides (TG) were measured using automated analyser. Statistical analysis was done using student 't' test. Pearson's correlation was performed to establish the relationship between study variables. Results: The plasma total cholesterol, TG, LDL, VLDL and HDL levels were significantly reduced in patients with OSMF as compared to the control group.(p<0.005). Conclusion: Our study indicates that there is an inverse relationship between OSMF and serum lipid profile. Decrease in the lipid levels may be considered as a valuable biochemical marker in the early diagnosis and prognosis of oral malignancy. [ABSTRACT FROM AUTHOR]