Abstract Background Numerous studies have shown that Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can infect immunocompetent patients simultaneously with other agents. Nonetheless, multiple infections with other agents in EBV/CMV-infected children have received little attention. We conducted a retrospective study of children with suspected infectious mononucleosis. Peripheral blood samples were analyzed by indirect immunofluorescence to detect EBV, CMV and other respiratory agents including respiratory syncytial virus; adenovirus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; Chlamydia pneumonia e and Mycoplasma pneumoniae . A medical history was collected for each child. Results The occurrence of multipathogen infections was 68.9%, 81.3% and 63.6% in the... children with primary EBV, CMV or EBV/CMV, respectively, which was significantly higher than that in the past-infected group or the uninfected group ( p < 0.001). Of the multipathogen-infected patients, the incidence of C. pneumoniae in children with primary infection was as high as 50%, significantly higher than in the other groups ( p < 0.001). In the patients with multipathogen infection and EBV/CMV primary infection, fever, rash, lymphadenopathy, hepatomegaly, splenomegaly, atypical lymphocytes and abnormal liver function were more frequent and the length of hospital stay and duration of fever were longer than in other patients. Conclusion Our study suggests that there is a high incidence of multipathogen infections in children admitted with EBV/CMV primary infection and that the distribution of these pathogens is not random.