CD163, a hemoglobin scavenger receptor for haptoglobin-hemoglobin complexes, is expressed by monocytes/macrophages and is often shed as soluble CD163 (sCD163) in response to inflammatory stimuli. This scavenger receptor is reported to dampen the inflammatory response, and high plasma levels of sCD163, which are thought to reflect the total level of CD163 expression, may predict the severity of disease. To understand the role of sCD163 in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS) better, the concentrations of sCD163 in plasma from 66 patients were quantified, and the relationships between sCD163 level and disease course, severity, and clinical parameters were analyzed. The level of plasma sCD163 in HFRS patients was elevated from fever onset and during the course of the disease, and it peaked in the oliguria stage at 874.5 (549.9-1138.0) ng/mL compared with controls at 192.8 (54.9-282.1) ng/mL. The correlations between plasma sCD163 and renal dysfunction suggest that sCD163 may play an important role in the development of acute renal failure in patients infected with Hantaan virus.