The glycoprotein gp130 is a signal traducing subunit with a membrane domain of the IL-6 receptor. In addition, gp130 is shared among the receptors for IL-6 superfamily, and it is critically involved in generating signal transduction through these receptors. The aim of the study is to evaluate the expression of the IL-6 superfamily receptor molecule gp130 on TCD4+ and B cells in patients with systemic lupus erythematosus (SLE). Surface expression of gp130 on TCD4+ and B lymphocytes was higher in patients with SLE than in healthy controls (2.79 vs 0.36% and 8.36 vs 0.37%, respectively). Patients with active lupus had higher expression of gp130 (relapsed 15.1%, new onset 26.6%) than stable patients (2.83%), in B-cell subset, but not in TCD4 lymphocytes. An important reduction in the gp130 expression on B lymphocytes was observed when the activity of the disease had disappeared after readjusting its immunosuppressive treatment (20.8–3.8%). In addition, there was significant correlation between the activity of the disease, measured like systemic lupus erythematosus disease activity index score, and surface expression of gp130 in lymphocytes B ( rs = 0.5880, P = 0.0002). According with our results and roc curve analysis, a cut-off in 6.7% of B cells with gp130 expression were defined, who discriminates active/stable SLE with a sensitivity of 0.93 and a specificity of 0.75. In conclusion, there is an altered expression of gp130 in the patients with SLE. The disease activity as well as immunotherapy seems to influence the pattern of expression of gp130 on B-cell subsets in patients with SLE.