B cells are essential players in the pathogenic mechanisms of systemic lupus erythematosus (SLE). Although CD5+ B cells have been considered to play a paradoxical role in preventing, rather than inducing autoimmunity, there is no consensus agreement about the proportions of CD5+ B cells population in SLE patients. So, the aim of the present study was to assess blood concentration of CD5+ B cells in patients with SLE and to evaluate their relationship with disease activity and organ damage. We recruited 100 SLE patients and 100 healthy control subjects. Based on SLE disease activity index (SLEDAI), patients were divided into two groups: active SLE (n = 50) and inactive SLE (n = 50). SLE was active when SLEDAI was ≥ 4. The expression of CD5+ B cells was evaluated using flow cytometry to measure the proportions and absolute numbers of the cells. The proportions of CD5+ B cells of total lymphocytes were significantly lower in SLE patients versus controls (4.1 ± 3.9 vs 10.8 ± 5.2%, P = <0.001). CD5+ B cells were significantly decreased in active SLE patients (3.1 ± 2.7%) in comparison to inactive patients (5.2 ± 3.7%) (P = 0.013). CD5+ B cells correlated positively with C3 (r = 0.328, P = 0.020) and C4 (r = 0.355, P = 0.011). CD5+ B cells were significantly decreased in SLE patients compared to healthy controls and they were significantly decreased in active SLE patients in comparison to inactive ones.