Abstract Between 2022 and 2025, high pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b was detected in poultry and wildlife across most countries in Central and South America . The epizootic peaked in 2023, subsided in 2024, and resurged in 2025 . In Central America , outbreaks in wildlife were few and small, and mostly affected pelicans . In contrast, South America experienced unprecedented mass mortality in colonial seabirds and pinnipeds , including endangered and endemic species. Notably, viral adaptation enabled mammal-to-mammal transmission in pinnipeds and rapid viral spread across multiple countries along the Pacific and Atlantic coasts . Subsequent introductions to subantarctic islands and Antarctica stemmed from South American viruses. In February 2025, a novel reassortant virus emerged, recombining HPAI H5N1 B3.2 genotype with South American low pathogenicity avian influenza viruses . In May 2025, HPAI H5N1 viruses re-emerged in Brazil , causing a series of outb...