CD163 is a 130-kDa, type I transmembrane protein belonging to group B of the cysteine-rich scavenger receptor family. Expression of CD163 is constitutive and/or induced by some stimuli on circulating monocytes and most tissue macrophages. An approximately 130-kDa soluble form of human CD163 is released from the cell surface by proteolysis after oxidative stress or inflammatory stimuli. Thus, an elevated level of circulating soluble CD163 (sCD163) has been reported in diabetes mellitus, which is one of the oxidative conditions. We have already acknowledged that scleroderma (SSc) is one of the oxidative conditions. Therefore, we conducted the measurement of serum sCD163 in SSc patients. After receiving the informed consents, 56 SSc patients were examined; 20 dermatomyositis patients were used as disease controls and 40 persons were used as healthy controls. Blood samples were collected, and the concentration of serum sCD163 was measured by ELISA (human CD163, R&D Systems). Other parameters in the blood of SSc patients were also examined. Statistical analyses were performed using Mann–Whitney U test, and the relationship between parameters was statistically examined by Spearman's rank test. Serum sCD163 levels were elevated in SSc patients compared with normal controls (p < 0.01), with similar levels between limited SSc and diffuse SSc patients. SSc patients with pulmonary fibrosis had increased serum levels of sCD163 than those without pulmonary fibrosis (p < 0.05). SSc patients with elevated sCD163 levels had increased serum levels of IgG than those with normal sCD163 levels (p < 0.05). Serum sCD163 levels correlated positively with pulsatility index in SSc patients (p = 0.0009, r = 0.534). These results suggest that oxidative stress may play an important role in immunological abnormalities, renal circulation, and pulmonary fibrosis of SSc.