Objective To investigate the correlations of postoperative serum levels of soluble CD40 ligand (sCD40L) and CC-chemokine ligand 3 (CCL3) with postoperative deep venous thrombosis (DVT) in patients with multiple rib fractures. Methods A total of 110 patients with multiple rib fractures were selected as the study subjects and divided into non-DVT group (n=79) and DVT group (n=31) based on the occurrence of postoperative DVT. Enzyme-linked immunosorbent assay was used to determine the expression levels of serum sCD40L and CCL3. Pearson correlation analysis was employed to analyze the correlations of serum sCD40L, CCL3 with coagulation function indicators. Logistic regression analysis was conducted to identify the influencing factors of postoperative DVT in patients with multiple rib fractures. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of serum sCD40L and CCL3 for postoperative DVT. Results The expression levels of serum sCD40L and CCL3 in the DVT group were significantly higher than those in the non-DVT group (P < 0.05). There were statistically significant differences in D-dimer, prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) between the two groups (P < 0.05). In the DVT group, serum levels of sCD40L and CCL3 were positively correlated with D-dimer and FIB, and negatively correlated with PT, TT and APTT (P < 0.05). D-dimer, PT, APTT, FIB, sCD40L and CCL3 were identified as influencing factors for postoperative DVT in patients with multiple rib fractures (P < 0.05). The area under the curve (AUC) of serum sCD40L and CCL3 alone for predicting postoperative DVT in patients with multiple rib fractures was 0.753 and 0.754, respectively, which was significantly smaller than 0.863 of their combined prediction (P < 0.05). Conclusion Postoperative DVT in patients with multiple rib fractures is associated with high levels of serum sCD40L and CCL3, which have certain predictive value for postoperative DVT.