Recent researches suggest that imbalance in apoptotic process may lead to susceptibility to systemic lupus erythematosus (SLE). Production of pro-inflammatory cytokines, such as IL-18, has important role in autoimmune process in lupus. There are cumulative data on the pro-apoptotic role of IL-18, in the Fas-mediated apoptosis. Soluble Fas (Apo/1-CD95) is a marker of apoptosis that appears to increase in serum of SLE patients. Previous studies demonstrated increasing serum concentrations of soluble Fas (sFas) and IL-18 in SLE. To assess the correlation between serum concentrations of sFas and IL-18 in SLE patients, 114 SLE patients were selected randomly at the different stages of disease activity according to SLEDAI2K. IL-18 and sFas serum concentrations were compared in patients and fifty randomly selected healthy volunteers. The correlations of IL-18 and sFas serum concentrations with SLEDAI2K and with each other were evaluated in patients. There were a significant difference between serum concentrations of sFas and IL-18 in the case and control groups (P = 0.001). There was a significant correlation between serum concentrations of sFAS and IL-18 in SLE patients (P < 0.0001, r = 0.411). The elevations of IL-18 and sFas(Apo/1-CD95) serum concentrations in SLE patients are significantly correlated.