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Background Epstein–Barr virus (EBV) infection exhibits considerable heterogeneity in clinical manifestations among children, ranging from self-limiting symptoms to severe complications. The role of viral load in disease progression remains incompletely understood. Objective To investigate the relationship between EBV DNA load levels and clinical characteristics, treatment response, and prognosis in pediatric patients. Methods A total of 192 children diagnosed with EBV infection and admitted to our hospital between January 2022 and October 2025 were included in the final analysis. Based on plasma EBV DNA levels at admission, patients were stratified into a high viral load group ( n = 99) and a low viral load group ( n = 93). Baseline clinical data, treatment regimens, virological and serological dynamics, incidence of complications, and length of hospital stay were collected and compared between the two groups. A multivariate Cox proportional hazards regression model was employed to identify independent factors influencing hospitalization duration. Results Comparative analysis of baseline characteristics revealed that the high viral load group exhibited significantly elevated peak alanine aminotransferase (ALT) ( p < 0.001), peak aspartate aminotransferase (AST) ( p < 0.001), and proportion of atypical lymphocytes ( p = 0.036) relative to the low viral load group. Regarding treatment, glucocorticoid administration was more frequent in the high viral load group ( p = 0.002), and the duration of hospitalization was prolonged ( p < 0.001). Virologically, EBV DNA levels were higher in the high viral load group both at admission (all p < 0.001), with significant reduction observed in both groups by discharge (all p < 0.001). The incidence of overall complications ( p < 0.001) and splenomegaly ( p = 0.001) was greater in the high viral load group. Multivariate Cox regression analysis, with hospitalization duration as the dependent variable, identified high viral load (HR = 0.528, p < 0.001) and splenomegaly (HR = 0.665, p = 0.016) as independent predictors of prolonged hospital stay. Conclusion High EBV DNA load is independently associated with more severe hepatic injury, increased risk of complications, greater need for immunomodulatory therapy, and extended hospitalization. Viral load monitoring may facilitate early identification of children at high risk of unfavorable clinical outcomes.