Imbalance between oxidative stress and helper T-cell (Th1)-derived cytokines is one possible cause for the pathogenesis of systemic lupus erythematosus (SLE). To evaluate the correlation between oxidative stress and Th1 cytokine level with the disease activity of SLE in the North Indian population, oxidative/anti-oxidant profiles: malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and interferon (IFN)-gamma, interleukin (IL)-12 were studied. The estimation of oxidant and anti-oxidant enzymes was done in erythrocyte hemolysate and the levels of IFN-gamma and IL-12 were determined in the culture supernatant of peripheral blood mononuclear cells (PBMC) by a sandwich enzyme-linked immunosorbent assay (ELISA). A significant increase in the level of lipid peroxidation, measured as malondialdehyde (MDA), was found in SLE patients. The activities of anti-oxidant enzymes: SOD, CAT, GPx and anti-oxidant molecule GSH were significantly reduced in SLE patients as compared to controls. Increased levels of IFN-gamma and IL-12 were found in the culture supernatant of PBMC of SLE patients. MDA level was positively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, IFN-gamma, IL-12 and negatively correlated with GSH in SLE patients. Strong positive correlations of IFN-gamma and MDA with SLEDAI score suggest that lipid peroxidation and pro-inflammatory cytokine, both are involved in the pathogenesis of SLE. Collectively, this study advocates that severity of disease might be enhanced by imbalance between oxidative stress and helper T-cell (Th1)-derived cytokines in SLE.