Objective: This study aims to investigate the correlation between blood leukocyte, CRP, LDH, and cytokine levels and the severity of illness in children with adenovirus pneumonia. Methods: A total of 100 children with adenovirus pneumonia (55 mild cases and 45 severe cases) who were treated at Guangzhou Women and Children’s Medical Center from January 2022 to January 2024, and 40 healthy children as a control group, were selected. Clinical data, some laboratory test data, and serum cytokine levels detected by flow cytometry were collected, and statistical methods were used to analyze the correlation between relevant indicators and the severity of the illness. Results: The research showed that among general clinical manifestations, the proportions of children with fever, dyspnea, pleural effusion, and moist rales in the severe group were all higher than those in the mild group (p < 0.05). Among the collected laboratory test data, indicators such as WBC, neutrophils, and LDH were significantly higher than in the mild group and the control group (p < 0.05) and were positively correlated with the severity of the disease. Regarding the tested cytokines, most children with adenovirus pneumonia showed elevated levels, and cytokines such as IL-6, IL-2, and IL-8 were significantly positively correlated with the disease. In the ROC curve analysis, NEU 6.03 × 10⁹/L (sensitivity 82.2%, specificity 72.7%, AUC 0.830) and IL-6 41.823 pg/mL (sensitivity 75.6%, specificity 81.8%, AUC 0.833) demonstrated certain value in the early identification of children with severe disease. Conclusion: In this study, laboratory indicators (C-reactive protein, lactate dehydrogenase, neutrophils, etc.) and changes in the levels of specific cytokines (TNF-β, IL-2, IL-6, IL-8, etc.) in children with adenovirus pneumonia were closely related to the severity of the disease. Notably, neutrophil count and interleukin-6 were significantly positively correlated with disease severity and had high AUC values, suggesting they may be important parameters for early prediction of the progression of mild adenovirus infection to severe disease.