Objectives: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by antibody formation against nuclear autoantigens. A receptor for Advanced Glycation (RAGE) is produced by many immune system cells, such as neutrophils, macrophages, and T cells, and interacts with many classes of ligands. In light of these results, the level of sRAGE, the soluble form of RAGE, may be associated with disease activity. In light of this information, we aimed to evaluate whether there is a relationship between plasma sRAGE levels and SLE. Materials and Methods: Eighteen patients diagnosed with SLE (M/F: 1/17) and twenty-one patients without any disease diagnosis (M/F: 2/19) were included as the control group. In these patients, plasma sRAGE level was measured by ELIZA method using an ELIZA (enzyme-linked immunosorbent assay) kit (BioVendor Research and Diagnostic Products). The data obtained were compared between the groups. Results: The mean plasma sRAGE level was lower in patients with SLE than in healthy control patients but not statistically significant (p=0.966). Our study found a positive correlation between SLEDAI and sRAGE levels in patients with SLE (r=0.628, p=0.005). Although no significant correlation was found between patients with SLE, sRAGE levels were positively correlated between fourteen patients classified as active SLE and the control group. Conclusions: In our study, we found that plasma sRAGE levels in patients with SLE were lower than in healthy controls, but plasma sRAGE levels in patients with active SLE were higher than plasma sRAGE levels in patients with inactive SLE. We hypothesized that reduced sRAGE levels in patients with SLE could be explained by the depletion of this soluble receptor. Our study differed from another similar study showing that blood sRAGE levels were higher in patients with SLE than in healthy controls. Blood sRAGE levels were significantly increased during active disease compared with patients with quiescent SLE.