Objective: To study the levels and clinical significance of high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC) and interleukin (IL)-6 in neonatal pneumonia. Methods: A retrospective analysis was conducted on case data of 150 children with neonatal pneumonia admitted to the hospital from January 2022 to May 2025. According to the type of infection, 86 children with bacterial infection were included in group A, and 64 children with non-bacterial infection were set as group B. 100 healthy children who received physical examination during the same period were selected as control group. The differences in serum hs-CRP, WBC and IL-6 levels among the three groups were observed, and receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of the above indexes on bacterial infection of neonatal pneumonia. Results: There were significant differences in serum IL-6, WBC and hs-CRP levels among the three groups (P<0.05). The levels of serum IL-6, WBC and hs-CRP in group A were significantly higher than those in group B (P<0.05). Drawing ROC curve showed that the areas under the ROC curves (AUCs) of serum IL-6, WBC and hs-CRP in the diagnosis of bacterial infection of neonatal pneumonia were 0.833, 0.799 and 0.873 respectively. The AUC of the combined diagnosis was 0.944. Conclusion: The levels of serum IL-6, WBC and hs-CRP in children with bacterial infection of neonatal pneumonia reveal increasing trends. The above three indexes have certain diagnostic value on bacterial infection of neonatal pneumonia, and the combined diagnostic value is the highest.