Abstract Highly pathogenic avian influenza (HPAI) viruses of H5N1 clade 2.3.4.4b, are spreading worldwide , posing a threat to wildlife, domestic animals, and humans . In 2025, a multidisciplinary collaboration for HPAI H5N1 surveillance among birds within Galveston County, Texas , was initiated. Between November and December 2025, oropharyngeal and cloacal swabs were collected from wild and domestic birds reported as dead or dying by Galveston County residents . Specimens were studied with molecular assays, Sanger sequencing, virus isolation, and next-generation sequencing. Molecular evidence of HPAI H5N1 was detected in 7 of 10 (70%) birds, and the virus was successfully cultured in MDCK cells . Next-generation sequencing analysis of eight influenza A genome segments demonstrated a 4:4 gene segment reassortant constellation within clade 2.3.4.4b, consistent with genotype D1.1. Community members exposed to HPAI were offered antiviral prophylaxis . No human infections were identi...