Objective To investigate the expression levels and significance of serum circular RNA Pumilio RNA binding family member 1 (circPUM1) and interleukin-27 (IL-27) in patients with chronic osteomyelitis (COM). Method A total of 90 COM patients admitted to our hospital from January 2021 to January 2023 were selected as the research objects (COM group), and were divided into grade Ⅰ (23 cases), grade Ⅱ (31 cases), grade Ⅲ (20 cases) and grade Ⅳ (16 cases) according to their severity. According to the prognosis, the patients were divided into good prognosis group (61 cases) and poor prognosis group (29 cases), and 60 healthy subjects were selected as the control group. The differences in the expression levels of serum circPUM1,IL-27,C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in each group were detected and compared, and the relationship between each index and the prognosis of COM patients was analyzed. Results The expression levels of serum circPUM1,IL-27, CRP and ESR in the COM group were significantly higher than those in the control group (all P＜0.001). The serum levels of circPUM1 and IL-27 in COM patients increased with the increase of grade, and the differences were statistically significant (all P＜0.001). The expression levels of serum circPUM1 and IL-27 in the poor prognosis group were significantly higher than those in the good prognosis group (P＜0.001, P=0.001).Logistic multivariate regression analysis showed that circPUM1 (OR=1.107, P＜0.001), IL-27 (OR=1.142, P＜0.001) and COM grade (OR=1.541, P＜0.001) were independent risk predictors of poor prognosis in patients with COM.The receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) predicted by circPUM1 and IL-27 for poor prognosis in COM patients were 0.798 and 0.848, respectively. The AUC predicted by circPUM1 combined with IL-27 was 0.916, which was higher than that predicted by circPUM1 and IL-27 alone (both P＜0.001). Conclusion The expression levels of circPUM1 and IL-27 in serum of COM patients are significantly increased. The abnormal expression levels of circpUM1 and IL-27 can reflect the severity of the disease and have a high predictive value for the prognosis of patients