Objective To explore the efficacy of imipenem/cilastatin （IPM/CS） in combination with thymalfasin in the treatment of elderly patients with severe pneumonia （SP）， and to analyze its impact on the pulmonary oxygenation function and the levels of serum soluble hemoglobin scavenger receptor 163 （sCD163）， soluble CD40 ligand （sCD40L）， and amyloid A （SAA） in these patients. Methods A total of 102 elderly patients with SP （senile pneumonia， presumably， though not clearly defined in this context） who were admitted to Qingdao Central Hospital， University of Health and Rehabilitation Sciences between January 2024 and August 2025 were randomly divided into the study group （n = 51， treated with IPM/CS + thymalfasin） and the control group （n = 51， treated with IPM/CS） using the random-number table method. The therapeutic effects were evaluated two weeks after the treatment. The regression time of symptoms and signs， the clinical pulmonary infection score （CPIS） before and after treatment， pulmonary oxygenation function ［including peripheral blood oxygen saturation （SpO2）， arterial partial pressure of oxygen （PaO2）， and oxygenation index （OI）］， immune function （CD3⁺， CD4⁺， CD4⁺/CD8+）， serum levels of C-reactive protein （CRP）， sCD163， sCD40L， SAA， and adverse reactions were recorded and compared. Results The study group exhibited a higher total effective rate （94.12% vs. 80.39%） （P < 0.05）， along with an earlier regression time of symptoms and signs （P < 0.05）. When compared with the pre-treatment values， the CPIS score， serum CRP， sCD163， sCD40L， and SAA levels in both groups decreased after treatment， whereas SpO₂， PaO₂， OI， CD3⁺， CD4⁺， and CD4⁺/CD8⁺ increased. Furthermore， the extent of decrease or increase in the above-mentioned indicators in the study group was more significant than that in the control group， and these differences were statistically significant （P < 0.05）. There was no significant difference in adverse reactions between the two groups （P > 0.05）. Conclusions The treatment of elderly patients with SP using IPM/CS in combination with thymalfasin is both safe and effective. This treatment approach can effectively enhance the pulmonary oxygenation function and immune function of patients， reduce the levels of serum sCD163， sCD40L and SAA， and shorten the regression time of symptoms and signs.