Objective To analyze the efficacy of montelukast sodium combined with N-acetylcysteine in the treatment of children with respiratory syncytial virus (RSV) lower respiratory tract infection.Methods The 100 children with RSV lower respiratory tract infection admitted to our hospital from July 2024 to August 2025 were randomly divided into a control group and an experimental group, with 51 and 49 cases in each group, respectively. The control group received montelukast sodium (4 mg orally, once daily). The experimental group received additional N-acetylcysteine (aerosol inhalation, once daily) besides the control group's treatment. Both groups were treated for one week. The relief times of signs and clinical symptoms, immune function, pulmonary function, inflammatory response, clinical efficacy, and adverse reactions were compared between the two groups.Results The relief times of dyspnea, shortness of breath, decreased percutaneous oxygen saturation, and wheezing symptoms were significantly shorter in the experimental group than in the control group (P < 0.05). Before treatment, no significant differences were observed between the control and experimental groups in CD4⁺ T-cell levels, CD3⁺ T-cell levels, CD4⁺/CD8⁺ ratio, forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), maximum voluntary ventilation (MVV), serum amyloid A (SAA), substance P (SP), or interleukin-10 (IL-10) levels (P > 0.05). After treatment, the experimental group showed significantly higher CD4⁺ T-cell levels, CD3⁺ T-cell levels, CD4⁺/CD8⁺ ratio, MVV, FVC, FEV₁, and IL-10 levels than the control group (P < 0.05), whereas SAA and SP levels were significantly lower in the experimental group (P < 0.05). The pre- to post-treatment changes in CD4⁺ T-cell levels, CD3⁺ T-cell levels, CD4⁺/CD8⁺ ratio, MVV, FVC, FEV₁, and levels of SAA, SP, and IL-10 were greater in the experimental group than in the control group (P < 0.05). The overall response rate was higher in the experimental group than in the control group (P < 0.05). No significant difference was found in the overall incidence of adverse reactions between the two groups (P > 0.05).Conclusion The combination of montelukast sodium and N-acetylcysteine demonstrates favorable therapeutic efficacy in children with RSV lower respiratory tract infection. It can significantly accelerate the resolution of clinical symptoms, improve pulmonary ventilation function and immune indicators, and effectively suppress the release of serum inflammatory mediators, without causing serious drug-related adverse events during treatment.