Background And Objectives: Oral cancer is one of the major forms of cancer worldwide and is one of the most common malignancies in India. The important initiators of oral cancer in India are tobacco consumption in various forms, with prevalence of smokeless tobacco (ST) use being 20% of the population. It is also known as chewing tobacco, oral tobacco, spit or spitting tobacco. It contains many carcinogens and mutagenic chemicals which are addictive. It generates reactive oxygen species (ROS) that include oxygen derived free radicals. Most free radicals are highly reactive and short-lived. They mediate oxidative degradation of lipid and produce various end products which results in cell damage, and one such end product is Malondialdehyde (MDA). MDA is considered to be crucial for development of potentially malignant lesions and cancer by forming adducts with DNA. Studies have shown a significantly high level of serum and salivary MDA in oral pre cancer and cancer. Correlation between serum and salivary MDA levels in tobacco chewers without lesions and with lesions are sparse. Limited research is available in tobacco chewers without lesions hence present study was done to evaluate both serum and salivary MDA levels in tobacco chewers with and without lesions and controls and to correlate the same Methods: 40 tobacco chewers without lesions, 40 tobacco chewers with lesions (20=Leukoplakia and 20 =OSCC) and 40 healthy controls were included in this study. Blood and saliva was collected by appropriate methods and analyzed for Malondialdehyde levels in both. Obtained serum and salivary MDA levels in cases and controls were compared and correlated by Pearson’s correlation analysis XII. Results: 1. Both serum and salivary MDA levels were higher in males than in females in cases and controls. 2. Serum and salivary MDA levels were raised in tobacco chewers without lesions 3. Serum and salivary MDA levels were significantly high in tobacco chewers with lesions (OSCC and Leukoplakia) than in the tobacco chewers without lesions 4. Tobacco chewers with OSCC had increased serum and salivary MDA levels than tobacco chewers with leukoplakia 5. No correlation was found between salivary MDA levels and serum MDA levels in controls and tobacco chewers with leukoplakia, however positive correlation was found with tobacco chewers without lesions and tobacco chewers with OSCC. Conclusion: The result indicates that, the antioxidant capacity of both blood and saliva will be reduced in tobacco chewers with and without leukoplakia or OSCC patients, which can be attributed to an increased oxidative stress. It also suggests that, as correlation between serum and salivary MDA levels showed varied results, stronger correlation studies with larger sample size are necessary to establish use of saliva as a reliable, oxidative stress marker.