Objective To investigate the correlation between the levels of activated protein C （APC）， thromboxane B2 （TXB2）， and soluble B7?H3 （sB7?H3） in the peripheral blood of elderly patients with pneumonia and the severity as well as prognosis of the disease. Methods One hundred elderly pneumonia patients admitted to our hospital from March 2022 to June 2024 were enrolled as the study group， and 100 healthy volunteers during the same period were selected as the control group. The levels of APC， TXB2， and sB7?H3 in peripheral blood were compared between the two groups. Study group patients were further categorized into low?risk， medium?risk， and high?risk subgroups based on the CURB?65 score （Confusion， Uremia， Respiratory rate， Blood pressure， Age ≥ 65 years）. The levels of APC， TXB2， and sB7?H3 in peripheral blood were compared among patients with varying disease severities. Pearson correlation analysis was performed to evaluate the correlation between the levels of APC， TXB2， and sB7?H3 in peripheral blood and disease severity. The study group was followed up for 30 days and subsequently divided into good prognosis and poor prognosis subgroups according to their clinical outcomes. Clinical data and peripheral blood levels of APC， TXB2， and sB7?H3 were compared between patients with different prognoses. Partial correlation analysis was conducted to assess the relationship between peripheral blood levels of APC， TXB2， and sB7?H3 and prognosis. Finally， the predictive value of these biomarkers was evaluated using the Receiver Operating Characteristic （ROC） curve. Results The level of APC in the peripheral blood of the study group was significantly lower than that of the control group， whereas the levels of TXB2 and sB7?H3 were significantly higher （P <0.05）. The severity of the disease in the study group was assessed using the CURB?65 score， which categorized patients into 33 mild cases， 39 moderate cases， and 28 severe cases. Severe patients exhibited a lower level of APC in peripheral blood compared to moderate and mild patients. Additionally， the levels of TXB2 and sB7?H3 in moderate patients were higher than those in mild patients， while severe patients demonstrated even higher levels of TXB2 and sB7?H3 compared to both moderate and mild patients （P < 0.05）. Pearson correlation analysis revealed that peripheral blood APC was negatively correlated with the CURB?65 score， whereas TXB2 and sB7?H3 were positively correlated with the CURB?65 score （P < 0.05）. During a 30?day follow?up period， the research team identified 79 patients with good prognoses and 21 patients with poor prognoses. Significant differences were observed in diabetes prevalence， disease severity， and APACHEⅡ scores between the poor prognosis subgroup and the good prognosis subgroup （P < 0.05）. The levels of APC in peripheral blood were significantly lower in the poor prognosis subgroup compared to the good prognosis subgroup， whereas the levels of TXB2 and sB7?H3 were significantly higher （P < 0.05）. Partial correlation analysis revealed that peripheral blood APC， TXB2， and sB7?H3 were significantly associated with prognosis （P < 0.05）. The AUC values for predicting the prognosis of elderly pneumonia patients using peripheral blood APC， TXB2， and sB7?H3 were 0.752， 0.738， and 0.761， respectively， with sensitivities of 66.67%， 76.19%， and 66.67%， and specificities of 78.48%， 67.09%， and 78.48%. When combining these three indicators for prognostic prediction， the AUC increased to 0.918， with a sensitivity of 85.71% and a specificity of 87.34%， demonstrating a significant improvement in predictive accuracy compared to each indicator used alone （Z = 2.207， 2.666， 2.109， P = 0.027， 0.008， 0.035）. Conclusion The levels of APC， TXB2， and sB7?H3 in the peripheral blood of elderly patients with pneumonia are significantly associated with the severity and prognosis of the disease. Combined detection of these biomarkers can serve as a reliable predictor of clinical outcomes.