Background: The most addictive constituent of tobacco is the alkaloid nicotine. Nicotine is said to have a considerable influence on the level of lipids in blood. Several studies have stated that alterations in lipid profile have been associated with development of OC and other premalignant lesions/conditions. Very little literature is available on lipid profile alterations at an early stage, i.e., before the development of OC. Aim: To assess and compare the lipid profile levels among tobacco chewers with and without leukoplakia. Materials & Methods: A total of 80 male subjects were included in the study and were randomly divided into two groups, Group I – 40 subjects (tobacco chewers without OL) and Group II – 40 subjects (tobacco chewers with OL). All the subjects who fulfilled the inclusion criteria were subjected to estimation of lipid profile. Results: The TC, HDL and LDL levels were higher, while TG and VLDL levels were lower in group II as compared to group I. Statistically significant difference was not noted between both the groups in relation to all the lipid parameters. The statistical analysis was carried out using Student’s unpaired t test and Chi – square test, with the help of Statistical Package for the Social Sciences (SPSS) 19 software. Conclusion: Thus, the lipid levels tend to increase in tobacco chewers and in subjects with OL, which can be an early change towards development of OC. This would help us in early diagnosis and prognosis of these lesions.