Abstract: Objective　To compare and analyze the clinical characteristics, diagnosis, and treatment of different subtypes of severe influenza in neonates to provide a reference for the diagnosis and treatment of neonatal severe influenza. Methods A cohort of 40 neonates with severe influenza who were hospitalized in the neonatology ward of Children's Hospital Affiliated to Zhengzhou University between January 2019 to December 2023 were selected and divided into two groups based on the virus subtype: influenza A (n=23) and influenza B (n=17). A retrospective analysis was conducted to compare general information, clinical manifestations, auxiliary examinations, complications, and treatment outcomes of neonates with severe influenza A and B infection. Results The number of days of hospitalization was longer in cases of influenza A than that of influenza B. The proportion of neonates with severe influenza A who exhibited fever was higher than that for influenza B, and a higher percentage of those with fever had peak temperatures ranging from 38.1 ℃ to 39 ℃. Gastrointestinal symptoms, including vomiting and diarrhea leading to dehydration, were more evident in severe influenza B cases. The proportion of influenza A cases with abnormal creatine kinase-MB isoenzyme levels (>25 U/L) was higher than that of influenza B, and the differences were statistically significant (P<0.05). There were no significant differences between the two types of influenza in other clinical manifestations, the incidence of pneumonia/respiratory failure complications, peripheral blood leukocyte count and classifications, the proportion of abnormal aspartate aminotransferase (AST) (>40 U/L), alanine aminotransferase (ALT) (>40 U/L), and creatine kinase (CK) (>200 U/L), and lactate dehydrogenase (LDH) values (all P>0.05). In terms of treatment, neonates treated with Oseltamivir within 48 hours of onset mainly suffered from influenza A. Among those treated with Oseltamivir, the proportion of influenza A cases whose body temperature returned to normal within 24 hours was relatively higher, whereas, for those whose temperature returned to normal within 24-72 hours, the proportion was relatively higher in influenza B cases. These differences were statistically significant (all P<0.05). Conclusions Severe neonatal influenza usually occurs in winter and spring. After severe infection, fever is more obvious in neonates with influenza A, which is more likely to cause myocardial cell damage. Neonates with influenza A can be treated with Oseltamivir earlier and return to normal body temperature faster than those with influenza B after Oseltamivir treatment. Gastrointestinal symptoms are more common in neonates with severe influenza B.