Objective: To explore changes of serum interleukin-6 (IL-6), interleukin-8 (IL-8) and serum amyloid A (SAA), and their relationship with disease severity in children with pulmonary infection. Methods: A total of 72 children with pulmonary infection and 72 healthy children in the hospital were enrolled as observation group and control group between June 2022 and June 2024, respectively. The levels of serum IL-6, IL-8 and SAA were compared between the two groups. According to disease severity, children with pulmonary infection were divided into severe group (n=23) and mild group (n=49), and levels of serum IL-6, IL-8 and SAA in the two groups were compared. The diagnostic value of IL-6, IL-8 and SAA in the severity of pulmonary infection was analyzed by receiver operating characteristic (ROC) curves. Results: The levels of IL-6, IL-8 and SAA were higher in observation group than control group (P<0.05). The levels of IL-6, IL-8 and SAA were higher in severe group than mild group (P<0.05). The results of ROC curves analysis showed that IL-6, IL-8 and SAA were all of diagnostic value in the severity of pulmonary infection, and diagnosis value of combined detection was higher (P<0.05). Conclusion: The levels of serum IL-6, IL-8 and SAA are increased in children with pulmonary infection. IL-6, IL-8 and SAA all have diagnostic value in the severity of pulmonary infection, and diagnosis value of combined detection is higher.