Shen-Ling-Bai-Zhu-San (SLBZS) is used for treating gastrointestinal disorders. However, the role of SLBZS in treating pneumonia in children is still unclear.In this study, children (≥2 and <9 years) with pneumonia were treated with 0.1 g cefixime (cefixime group) or 0.1 g cefixime + 9 g SLBZS (SLBZS + cefixime). The drugs were administered twice daily for 10 days. The therapeutic effects of the two groups were compared. The white blood cell (WBC), neutrophil, and lymphocyte counts; neutrophil-lymphocyte ratio (NLR); serum inflammatory factor levels; and gut microflora were assessed.The clinical efficacy of SLBZS + cefixime treatment of pneumonia in children was higher than that of cefixime alone (93.3% vs. 86.7%). Both cefixime and SLBZS + cefixime treatments decreased the area of pulmonary inflammatory lesions, reduced white blood cell and neutrophil counts, neutrophil-lymphocyte ratio, inflammation, and increased lymphocyte count in children with pneumonia compared with those before treatment. Moreover, SLBZS enhanced the anti-inflammation and immunity-enhancing effects of cefixime in children with pneumonia. SLBZS + cefixime treatment decreased Enterobacter, Enterococcus, Bacteroides, and Fusobacterium counts and increased Bifidobacterium and Lactobacillus counts. Compared with the cefixime treatment group, the count of the six bacterial strains in the SLBZS + cefixime treatment group was closer to the normal level.SLBZS enhanced the antipneumonia effect of cefixime in children with pneumonia by ameliorating gut microflora, inflammation, and immune response.Copyright © 2022 Jinli Feng et al.