Background: To investigate the value of serum monocyte chemotactic protein 1 (MCP-1) and soluble mannose receptor (sMR) for predictive diagnosis of pediatric sepsis. Methods: This study retrospectively analyzed the data of 82 children with acute and severe signs of inflammation. According to the diagnostic criteria of sepsis, these children were divided into a sepsis group (40 cases) and a non-sepsis group (42 cases). In addition, 50 children who received health examinations during the same time period in Cangzhou Central Hospital were selected as a control group. According to the prognosis of the children in the sepsis group, they were further divided into a survival group (33 cases) and a death group (7 cases). The levels of blood indicators, inflammatory markers, liver and kidney function indicators, MCP-1 level, and sMR were collected from the children. The efficacy of using sMR and MCP-1 levels in the predictive diagnosis of sepsis was analyzed by using the area under the ROC curve (AUC). Results: Serum levels of MCP-1 and sMR were (452.32±2.79) μg/ml and (97.23±.15) μg/ml, respectively, in the sepsis group, significantly higher than those in all controls (P<0.001). In the death group, the levels of white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), sMR, and MCP-1 were significantly higher compared to the survival group (P<0.05). The AUC for CRP in predictive diagnosis of sepsis was 0.9075; the AUC for PCT was 0.8759; the AUC for sMR was 0.9244; and the AUC for MCP-1 was 0.9406. Conclusions: Serum sMR and MCP-1 levels can help predict the diagnosis of pediatric sepsis.