Objectives: Assessment of upstream levels of lipid peroxidation and DNAdamage regulating the development of rheumatoid arthritis. Data Source: All the sampleswere collected from Jinnah Hospital Lahore. Study Design: Comparative cross sectional study.Period: Two years from 18-09-2014 to 24-10-2016. Setting: The Institute of Molecular Biologyand Biotechnology (IMBB) in The University of Lahore-Pakistan. Material and Methods:Blood, saliva and synovial fluid of fifty (n=50) individuals diagnosed with Rheumatoid Arthritisand fifty (n=50) age-sex matched controls were added in current study. Levels of MDA weredetermined spectrophotometrically while the concentrations of isoprostanes, 8-OHdG and4-HNE were measured by the help of commercially available Elisa Kit. Results: Levels oflipid peroxidation products including MDA (μmol/ml), isoprostanes (pg/ml), 4-HNE (μmol/ml)and DNA damage in the form of 8-OHdG (pg/ml) were significantly high (p<0.015, p<0.022,p<0.004 and p<0.036) in patients as relative to normal individuals. Levels of MDA in serum(1.95±0.094 vs. 0.95±0.019), saliva (0.012±0.0034 vs. 0.056±0.0056) and synovial fluid(3.26±0.65 vs. 0.019±0.0016) were differed significantly in each groups. Level of isoprostanesin serum (12.26±5.26 vs. 1.26±0.015), saliva (2.16±0.019 vs. 0.816±0.017) and synovial fluid(34.26±4.26 vs. 0.136±0.019) were recorded higher in RA patients as compared to control.Concentrations of 8-OHdG in serum (0.945±0.014 vs. 0.019±0.0035) saliva (0.0024±0.0003/0.0029±0.00017) and synovial fluid (1.33±0.451 vs. 0.055±0.0016) were recorded high in RApatients. Significantly higher concentration of 4-HNE in serum (4.265±1.25 vs. 1.99±0.016),saliva (1.26±0.15 vs. 0.191±0.0091) and synovial fluid (6.35±1.16 vs. 0.094±0.00165) wererecorded in patients with RA. Conclusion: Present study concluded the role of oxidativebiomarkers and their differential expression in the onset of autoimmunity in patients with RA.Increased stress is involved in the DNA damage and increased lipid peroxidation in the synovialfluid. Therefore, antioxidant therapy may have some prognostic role in the patients with RA bydecreasing the intensity of oxidative stress and DNA damage.