Objective To investigate the differences in clinical features and laboratory parameters of infectious mononucleosis (IM) caused by Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV) in children. Methods The data of 109 children with IM admitted to hospital from January 2018 to January 2023 were retrospectively analyzed, and they were divided into three groups: EBV infection group, CMV infection group, and mixed infection group. General characteristics, clinical manifestations and laboratory findings of children with IM in the infection group. Results A total of 109 cases of children with IM were collected in this study, including 61 males and 48 females, with a male to female ratio of 1.27〖DK〗∶1.The mean age was (4.66±2.68) years, and the incidence was more frequent in children aged 2 to 6 years, accounting for about 73.4%.Children of IM suffer from the disease all year round, with a relatively high number of cases in winter and spring, accounting for 58.7% of the total number of cases.The clinical manifestations of the children were varied, among which fever (94 cases, 86.2%), lymph node enlargement (85 cases, 78.0%), pharyngitis (82 cases, 75.2%), liver enlargement (53 cases, 48.6%) and cough (52 cases, 47.7%) were the most common. The incidence of lymph node enlargement and pharyngitis was significantly lower in the CMV-infected group than in the other two groups (P＜0.05)The incidence of abnormal WBC count, LY% and AL% was higher in the mixed infection group than in the other two groups, and the incidence of abnormal LDH, ALT and AST results was more significant in the mixed infection group (P＜0.05)Conclusion Mixed CMV and EBV infections in children have become more common in recent years. The clinical presentation is more like EBV infection, and the laboratory findings are more serious than those of single infections with EBV and CMV, requiring more attention