Aim: This study investigates serum interleukin(IL)-37 levels in patients with systemic sclerosis (SS) and assesses its relationship with clinical findings. Methods: This study included 35 patients with SS and 30 healthy control subjects. The demographic and clinical characteristics of the patients, such as the presence of Raynaud’s phenomenon, SS subtype, digital ulcers, gastrointestinal and lung involvement, and disease activity, were recorded. The medications used by the patients were recorded, and Serum IL-37 levels were measured using an enzyme-linked immunosorbent assay. The United Kingdom Functional Scoring system was used to evaluate the functional status of the patients, while the Valentini criteria were used to evaluate disease activity. Skin involvement was evaluated based on the modified Rodnan skin score. Results: Although serum IL-37 levels were found to be lower in patients with SS than in the control group, the difference was not statistically significant (p= 0.078). A negative correlation was identified between serum IL-37 levels and C3 levels in patients with SS (p= 0.046). No significant relationship was found between IL-37 levels and other clinical and laboratory parameters. Conclusion: Unlike in patients with autoimmune disorders, serum IL-37 levels were found to be lower in patients with SS than in the control subjects, and IL-37 demonstrated a negative correlation with C3 levels.