Abstract: OBJECTIVE To explore the epidemiological characteristics of respiratory tract infections with major pathogens in children in Southern Hainan Province. METHODS The results of submission and testing of respiratory tract pathogens were collected from the children with respiratory tract infections who were treated in outpatient department, emergency department and were hospitalized in Sanya Central Hospital from 2020 to 2025. The prevalence trends of the major species of pathogens causing the respiratory tract infections in the children of Southern Hainan Province were observed. RESULTS A total of 442 367 children with respiratory tract infections were enrolled in the study, with the median age 4 years old. Totally 171 890 case-times of children were submitted for testing, the total case-time submission rate was 38.86%, and the throat swab (52.17%) and serum (42.15%) were the major types of specimens. The submission rates of Chlamydia pneumoniae DNA and adenovirus DNA parallelly ranked the first place (5.05%), while the positive rate of C. pneumoniae DNA was low (0.49%), with the seasonal distribution steady. The positive rate of adenovirus was 16.82%, and the positive rate was 18.48% among the children with 3 to 6 years of age, it was prevalent in summer. The positive rate of SARS-CoV-2 nucleic acid testing was 6.33%, the positive rate was 9.39% among the children with more than 6 years of age, and it was highly prevalent in spring. The submission rates of respiratory syncytial virus (RSV) RNA and influenza A virus RNA did not rank in the front, but the positive rates were high, which were 18.28% and 16.46%, respectively; the RSV was highly prevalent in summer and autumn, while the influenza A virus was highly prevalent in autumn and winter. The submission rates of Mycoplasma pneumoniae DNA and IgM were 4.99% and 2.34%, respectively; the positive rates were 18.58% and 22.52%, respectively; the two testing items were basically same in population distribution and were prevalent in winter. The positive rate of bacterial and viral culture was 25.30%, the positive rate was 39.56% among the children with 0 to 1 year of age; Staphylococcus aureus, Klebsiella pneumoniae and Moraxella catarrhalis were dominant among the isolated bacteria. CONCLUSIONS There is regional difference in the prevalence trend among the respiratory tract pathogens. It is demonstrated that the M. pneumoniae is common in winter, while the viruses are prevalent in all the four seasons.