Objective To analyze the application effect of gamma globulin combined with antibiotic de-escalation therapy in pediatric severe pneumonia. Methods A total of 96 children with severe pneumonia admitted to Ruijin People's Hospital of Jiangxi Province from June 2020 to June 2021 were selected as the study objects, they were divided into study group and reference group according to random number table method, with 48 cases in each group. The reference group was treated with the antibiotic de-escalation therapy based on the basic symptomatic treatment measures, the study group was treated with gamma globulin combined with antibiotic de-escalation therapy based on the basic symptomatic treatment measures. After 6 d of drug administration, the treatment effect of the two groups were observed and analyzed, and the changes of inflammatory factors and immune function such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), immunoglobulin A (IgA) and immunoglobulin G (IgG) were measured in the two groups,and the total incidence of adverse reactions was counted and compared between the two groups. Results The total effective rate of the study group was higher than that of the reference group, the difference was statistically significant (P<0.05). There were no significant differences in hs-CRP, IL-6, IgA and IgG between two groups before treatment (P>0.05). After treatment, the hs-CRP and IL-6 of the two groups were lower than those before treatment, while IgA and IgG were higher than those before treatment, the differences were statistically significant (P<0.05). The hs-CRP and IL-6 of study group were lower than those of the reference group, IgA and IgG were higher than those of the reference group, the differences were statistically significant (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05). Conclusion The treatment of severe pneumonia in children with gamma globulin combined with antibiotic de-escalation therapy can improve the immune function of the body, improve the clinical efficacy, and promote the improvement of inflammatory factors. It has good safety and application effect.