Objective To analyze the disease burden and epidemic characteristics of major pathogens causing acute respiratory infection (ARI) in children in Guangzhou City. Methods In 2017.01-2022.06, 18 542 hospitalized children with ARI in a hospital in Guangzhou City were taken as the research objects. Serum IgM antibodies against 8 common pathogens, including respiratory syncytial virus (RSV), adenovirus (ADV), influenza virus A (IFV-A), influenza virus B (IFV-B), parainfluenza virus (PIV), Legionella pneumophila (LP), Mycoplasma pneumo-niae (MP) and Chlamydia pneumoniae (CP), were detected by indirect immunofluorescence method. SPSS 22.0 software was used for statistical analysis. Results The average length of hospital stay of 18 542 children with ARI was 7 days, and the median of total hospitalization expense was 5 870.93 Yuan. The total hospitalization expense of children in the -1-year-old group was the highest. Among 18 542 children, 10 214 were infected with at least one pathogen, with a detection rate of 55.09%. Detection rate in boys (52.31%) was lower than that in girls (59.77%). The total detection rate and co-infection rate in 2017-2019 were higher than those in 2020-2021, and those in elder group were higher than in younger group. 4 973 children were co-infected, mostly with IFV-A+IFV-B+MP (n=1 033) and IFV-A+IFV-B (n=1 022). The top three pathogens with the highest detection rates were IFV-B (27.27%), MP (25.47%) and IFV-A (21.24%). Detection rate of RSV decreased with the increase of age, and detection rate of LP, CP and MP increased with the increase of age. Detection rate of ADV peaked in children in the -3-year-old group, while detection rates of IFV and PIV were the highest in the -5-year-old group. CP and RSV occurred frequently in summer and autumn, however, detection rates of the other 6 pathogens showed no obvious seasonal dependence. Conclusion Pathogens causing ARI in children in Guangzhou City have different age di-stribution and seasonal epidemic characteristics. Measures should be taken to reduce the incidence of pneumonia in younger children, so as to ease their disease burden of ARI.