We aimed to assess the association between serum levels of soluble IL-2 receptor (sIL-2r) and endothelin-1 and severe infection in children with Crimean-Congo hemorrhagic fever (CCHF). Fifty-two patients under 18 years of age with a laboratory-confirmed diagnosis of CCHF and 38 healthy controls were enrolled in the study. Patients were classified into two groups based on disease severity (severe group and non-severe group). The sIL-2r and endothelin-1 levels were observed to be significantly higher in patients with severe CCHF compared with those with non-severe CCHF and the control group (p < 0.05). In addition, those with non-severe CCHF were also found to have a significantly higher sIL-2r level relative to the control group (p < 0.001). Although there was a positive correlation between sIL-2r and endothelin-1 levels, serum levels of both sIL-2r and endothelin-1 were negatively correlated with the platelets count. In children with CCHF, serum levels of sIL-2r and endothelin-1 were increased, and this increase is related to the severity of the disease. In this study, we concluded through prognosis that serum levels of sIL-2r and endothelin-1 might be related, and that hemophagocytic lymphohistiocytosis and endothelial injury might contribute to a pathogenesis of the disease.