Objective ·To detect the serum levels of high mobility group box 1 (HMGB1) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with multiple injuries at different time points, and to analyze their correlation with disease severity, complications and prognosis. Methods ·Ninety-two patients with multiple injuries admitted to the Department of Emergency Medicine of the Suzhou Ninth People′s Hospital from December 2020 to December 2022 were selected. According to the injury severity scores of the patients at admission, the patients were divided into light injury group (n=24), grave injury group (n=58) and severe injury group (n=10). According to whether there was multiple organ dysfunction syndrome (MODS) after admission, the patients were divided into MODS group (n=20) and non-MODS group (n=72). According to the outcome within 28 d after trauma, the patients were divided into death group (n=13) and survival group (n=79). Inflammatory factor indicators in venous blood of patients after admission were detected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sTREM-1 levels at 24 h, 72 h and 7 d after trauma, and the differences of serum HMGB1 and sTREM-1 levels among different groups were analyzed. Multiple Logistic regression was used to analyze the influencing factors of adverse outcomes in patients with multiple injuries. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HMGB1 and sTREM-1 for adverse outcomes. Results ·The levels of HMGB1 and sTREM-1 in the grave injury and severe injury groups were significantly higher than those in the light injury group (P<0.05). The levels of HMGB1 at 72 h and 7 d, and sTREM-1 at 24 h and 72 h in the severe injury group were significantly higher than those in the grave injury group (P<0.05). There was a positive correlation between HMGB1 and sTREM-1 levels at various time points (r=0.645, r=0.942, r=0.722; all P<0.05). The levels of HMGB1 at 72 h and 7 d, and sTREM-1 at 24 h and 72 h in the MODS group were significantly higher than those in the non-MODS group (all P<0.05). The levels of HMGB1 at 72 h and 7 d, and sTREM-1 at 24 h and 72 h in the death group were significantly higher than those in the survival group (all P<0.05). Logistic regression analysis showed that HMGB1 at 7 d, admission time and hypersensitive C-reactive protein (hs-CRP) were independent factors of adverse outcomes in patients with multiple injuries (all P<0.05). The ROC curve showed that the area under the curve of HMGB1 for predicting poor prognosis at 7 days after trauma was 0.890, the sensitivity was 83.5%, and the specificity was 92.3%. Conclusion ·The levels of HMGB1 and sTREM-1 are correlated with MODS and survival outcomes in patients with multiple injuries at different time points after trauma, and HMGB1 at 7 d after trauma is an independent factor affecting adverse outcomes in patients with multiple injuries.