Objective To investigate the clinical characteristics of infectious mononucleosis (IM) combined with Mycoplasma (MP) infection in children in different age period. Methods Data of children with IM who were admitted to the department of infectious diseases of a children's hospital between 2016 and 2018 were collected and divided into simple IM group and IM+MP infection group according to whether MP infection was complicated. Demographic characteristics were divided into infancy period (< 1 year old), early childhood period (1-3 years old), pre-school period (4-6 years old) and school-age period (7-13 years old) according to children's age. Clinical characteristics and laboratory data of two groups of children were analyzed. Results Among 750 hospitalized children with IM, 410(54.7%) were simply with IM and 340(45.3%) were with IM+MP, 44.8% (n=336) were in early childhood period, and 34.4% (n=258) were in pre-school period. The proportion of children in infancy period in IM+MP group was higher in spring and summer (41.7% for each) and lower in autumn and winter (8.3% for each); proportion of children in school-age period in IM+MP group in autumn was higher (42.3%). Compared with simple IM group, children in IM+MP group were more likely to develop blood system complication in infancy period, respiratory system diseases in early childhood period, and circulatory system diseases in pre-school period; occurrence rates of eyelid edema in infancy period, occurrence rates of pharyngeal secretion and hepatomegaly in early childhood period, occurrence rates of high fever and eyelid edema in pre-school period, as well as occurrence rates of high fever and splenomegaly in school-age period were all higher; In IM+MP group, alanine aminotransferase(ALT) in infancy period, white blood cell(WBC) in early childhood period, creatine kinase isoenzyme(CK-MB) in pre-school period, as well as WBC, ALT and Epstein-Barr virus DNA (EB-DNA) in school-age period were all higher than those in simple IM group; CD4⁺/CD8⁺ of two groups of children decreased gradually with the increase of age, which was more obvious in the pre-school and school-age IM+MP group, differences were all statistically significant (all P < 0.05). Conclusion Proportion of children with IM+MP in different age period is varied with different seasons. Compared with simple IM children, IM+MP group is different in complications, clinical characteristics and laboratory indicators, understanding the disease characteristics of different age groups is conducive to early diagnosis and rational treatment.