Objective To investigate the expressions and prognostic values of neutrophil elastase (NE) and vascular cell adhesion molecule-1 (VCAM-1) in children with severe pneumonia.Methods A total of 108 children with severe pneumonia admitted to our hospital from January 2020 to January 2022 were selected, and 96 healthy children who came to the hospital for physical examinations during the same period were selected. Serum levels of NE and VCAM-1 were compared between children with severe pneumonia and healthy children. After 21 days of follow-up, the survival of children with severe pneumonia was observed. The univariable analysis was performed to determine the factors affecting the death of children with severe pneumonia, which were further included for Logistic regression analysis. Pearson method was used to analyze the correlations between serum levels of NE and VCAM-1 and the Pediatric Critical Illness Score (PCIS) of children with severe pneumonia, and receiver operating characteristic (ROC) curve was applied to analyze the values of serum levels of NE and VCAM-1 for predicting the death of children with severe pneumonia.Results Serum levels of NE and VCAM-1 in children with severe pneumonia were higher than those in healthy children (P < 0.05). There was no difference in gender, age, pulmonary atelectasis, pleural effusion, drug treatment regimens, body temperature, heart rate, respiratory rate, fasting blood glucose, white blood cell count, neutrophil count, and levels of tumor necrosis factor-α, procalcitonin, and lactic dehydrogenase between the death group and the survival group (P > 0.05). The incidence of shock, the proportion of multi-lobar involvement, APACHE Ⅱ score, and the levels of C-reactive protein, NE and VCAM-1 were higher in the death group than those in the survival group (P < 0.05). The multivariable Logistic regression analysis showed that serum levels of NE [O^R = 3.762 (95% CI: 1.513, 9.354) ] and VCAM-1 [O^R = 3.622 (95% CI: 1.457, 9.006) ], APACHE II score [O^R = 3.267 (95% CI : 1.314, 8.124) ] and multi-lobar involvement [O^R = 3.200 (95% CI: 1.287, 7.955) ] were factors affecting the death in children with severe pneumonia (P < 0.05). The Pearson correlation analysis demonstrated that the serum levels of NE and VCAM-1 were both negatively correlated with PCIS of children with severe pneumonia (r = -0.373 and -0.544, both P < 0.05). The sensitivity, specificity, and the area under the ROC curve were 80.00% (95% CI: 0.593, 0.933), 97.59% (95% CI: 0.916, 0.998) and 0.919 (95% CI: 0.851, 0.963), respectively.Conclusions Serum levels of NE and VCAM-1 in children with severe pneumonia are abnormally elevated, both of which are closely related to the prognosis of these children. Thus, the serum levels of NE and VCAM-1 can be used as sensitive indicators to predict the death of children with severe pneumonia.