Recent animal studies have shown that CD4⁺CD25⁺ T cells play a crucial role in the suppression of the immune response and that depletion of this subset of T cells might lead to development of autoimmune diseases. The aim of the present study was to investigate the levels of CD4⁺CD25⁺ T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE). Ninety‐four SLE patients, 52 patients with rheumatoid arthritis (RA) and 50 age‐ and gender‐matched healthy individuals were enrolled in the study. A flowcytometric method was applied in the measurement of CD4⁺CD25⁺ T cells. The results showed that patients with SLE had statistically lower levels of CD4⁺CD25⁺ T cells than did normal controls, when expressed as either percentages of peripheral blood mononuclear cells (PBMCs) (mean ± SD, 8.49 ± 6.36 versus 11.11 ± 4.58%, P < 0.05) or absolute cell numbers (98.77 ± 97.52 versus 213.93 ± 104.52 cells/mm³, P < 0.05). In terms of CD25^brightCD4⁺ T cells, defined as having a fluorescence intensity of CD25 expression exceeding 100, SLE patients still had significantly lower levels than did normal controls expressed as percentages of PBMCs (1.76 ± 1.32 versus 3.73 ± 1.30%, P < 0.05). No significant differences could be found between RA patients and normal controls. The overwhelming majority of CD4⁺CD25⁺ T cells belonged to CD45RO⁺ cells and most did not express the CD69 molecule. Although decreased CD4⁺CD25⁺ T cells were found in SLE patients, we failed to find a significant correlation between the levels of CD4⁺CD25⁺ T cells and disease activities of SLE. To the best of our knowledge, this is the first study to demonstrate that patients with SLE had decreased CD4⁺CD25⁺ T cells. However, the exact role of the decreased CD4⁺CD25⁺ T cells in the pathogenesis of SLE remains to be elucidated.