In January 2025, the CDC reported several deaths among children under 18 from a severe form of influenza-associated encephalopathy (IAE) known as acute necrotizing encephalopathy (ANE). Due to a lack of national surveillance for IAE, the CDC requested clinicians and health departments to report U.S. pediatric IAE cases during the high-severity 2024-25 influenza season. Among 192 reports of suspected IAE, 109 cases were confirmed as IAE, with 37 classified as ANE. The median age of affected children was 5 years, and 55% were previously healthy. A significant 74% required intensive care, and the mortality rate was 19%, rising to 41% for ANE cases. Only 16% of eligible children had received the 2024-25 influenza vaccine. Health care providers are urged to consider IAE in children presenting with encephalopathy or altered consciousness after a febrile illness during influenza outbreaks. The CDC recommends annual influenza vaccination for all children aged 6 months and older to prevent influenza and its severe complications, including IAE and ANE.