ABSTRACT Capsule HPAI H5N1 was documented for the first time in the subantarctic region on Bird Island, South Georgia, resulting in the mortality of Brown Skuas Stercorarius antarcticus, Gentoo Penguins Pygoscelis papua, Snowy Albatrosses Diomedea exulans, and Antarctic Fur Seals Arctocephalus gazella. Aims The spread of the HPAI H5N1 subtype has had dramatic impacts on numerous populations of wild birds and mammals. We describe a case study that can inform the management of HPAI for conservation practitioners and researchers globally. Methods We documented the detection, monitoring, and impact of the first known outbreak of H5N1 HPAI in the subantarctic region, at Bird Island in South Georgia (−54.3582, −36.5112) during 2023–2024. Deaths from HPAI were first suspected in September 2023 and later confirmed by genetic analysis. Results In total, 77 Brown Skuas, 38 Gentoo penguins, and 58 Snowy Albatrosses were suspected to have died from HPAI infection, and HPAI was confirmed in 5 dead Antarctic Fur Seals. Total mortality was unknown for all species, as other individuals will have been scavenged before discovery, or died at sea. Conclusion This case study provides lessons for the management, risk, safety considerations, and ethical decisions regarding animal welfare that may help guide research and management responses to HPAI outbreaks elsewhere, particularly in remote areas or in species of conservation concern.