BACKGROUND Systemic Lupus Erythematosus (SLE) is a complex chronic immunological disease characterized by increased B cell activity and altered T cell function. OBJECTIVE To investigate relationship between T lymphocyte subsets and cortisol with the disease activity of systemic lupus erythematosus patients in North India. METHODS The percentage of CD4(+) and CD8(+) T cells in the lymphocyte of SLE patients and healthy controls were determined by flow cytometry. Serum cortisol of SLE patients and healthy controls was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS A significant decrease in the percentage of CD4(+) T cells and increase in the percentage of CD8(+) T cells were found in patients with SLE compared to the healthy controls. Decrease in the ratio of CD4(+)/CD8(+) T cell and low level of serum cortisol were found in the patients with SLE. The ratio of CD4(+)/CD8(+) T cell was inversely correlated with systemic lupus erythematosus disease activity index (SLEDAI) score and erythrocyte sedimentation rate (ESR). A positive correlation was observed between CD8(+) T cells and SLEDAI score. Furthermore, CD8(+) T cells were positively correlated with ESR in the patients with SLE. CONCLUSIONS The results showed that low level of cortisol and high percentage of CD8(+) T cells in the lymphocytes could be actively involved in the pathogenesis of SLE.