Objectives: The etiology and pathogenesis of systemic lupus erythematosus remains unknown, evidence exists for the involvement of mycobacterial antigen. This study is aimed to determine the effect of Mycobacterium tuberculosis on clinical course of SLE patients and the role of ROS and TNF-α in the pathogenesis of tuberculosis associated SLE patients. Methods: This study was done on 100 patients divided into SLE group (n=30), TB group (n=30), SLE-TB group (n=30) and control group (n=10). All patients underwent clinical, biochemical and immunological evaluation by employing techniques such as SDS-PAGE, direct binding and competition ELISA, PBMC and cell culture. Results: Fever, arthritis, skin rash, photosensitivity were more common in both SLE and SLE-TB group. Reduced glutathione showed amelioration of ROS and TNF-α induced action, which in turn, subsequently suppressed the immune-bindings observed in monocytes of TB and SLE patients cultured without glutathione. Conclusion: Data shows that SLE patients are more susceptible to developing Mycobacterium tuberculosis, as ROS and TNF-α in SLE patients could activate the replication of mycobacterial Ag85B (30 kDa) after bacilli infection