Cluster of differentiation 163 (CD163) is a receptor that binds haptoglobin-hemoglobin complexes and is mainly expressed on macrophages and monocytes. As a result of shedding, the extracellular portion of CD163 circulates in the blood as a soluble CD163 (sCD163). This study aimed to measure serum sCD163 levels in patients with systemic sclerosis (SSc) and to assess its association with the clinical, laboratory, and radiological features of the disease. Material and Methods: We measured serum sCD163 levels in 24 patients with SSc and in 30 healthy controls. Complete history of the patients was recorded and thorough clinical, rheumatological, and dermatological examinations were performed. For SSc, the skin thickness score was scored according to the modified Rodnan skin score method and pulmonary involvement was assessed in all patients using high-resolution computed tomography and by performing pulmonary function tests. Results: The mean serum sCD163 levels in patients with diffuse and limited SSc (61.64±19.57 and 60.8±21.43 ng/mL, respectively) demonstrated a highly statistically significant increase compared with the mean serum levels in healthy controls (36.97±16.37 ng/ mL) (p