Importance Since 1997, more than 1000 infections with highly pathogenic avian influenza A(H5N1) virus among humans have been reported globally. Given ongoing A(H5N1) outbreaks in animals, understanding the frequency of A(H5N1) virus infections among asymptomatic persons can inform public health risk assessments and infection prevention guidance.

Objective To identify and characterize reported cases of asymptomatic A(H5N1) virus infection among humans with confirmation by both molecular testing of 1 or more respiratory specimens and 1 or more serum specimens meeting World Health Organization criteria (molecularly and serologically confirmed [MSC]) or molecular confirmation (MC) alone.

Evidence Review MEDLINE, Embase, Global Health, Cochrane, Scopus, Virtual Health Library, and Europe PubMed Central were searched for publication through August 25, 2025. Articles for full-text screening were evaluated by 2 investigators. Studies published through August 25, 2025, were included if they reported a confirmed A(H5N1) virus infection that met MSC or MC criteria and had a full-text report in English. Articles were excluded if they reported results from A(H5N1) serologic testing alone, serosurveys, or other immunologic studies.

Findings Of 1567 unique reports that underwent title or abstract screening, 42 were selected for full-text screening, of which 10 met inclusion criteria (3 reports about 2 MSC cases and 7 reports about 16 MC cases). The 2 MSC cases occurred among adults in Pakistan and Vietnam who were identified by investigations of household contacts of index A(H5N1) case patients; 1 case patient also had exposure to A(H5N1) virus–infected chickens as the possible infection source and 1 is thought to have been infected through human-to-human transmission. Neither MSC case patient used personal protective equipment. Of 16 reported MC cases (14 adults, 2 children), 11 were identified by enhanced surveillance of persons exposed to A(H5N1) virus–infected poultry (8 in Bangladesh, 2 in Spain, and 1 in the UK) and the remaining 5 MC cases (3 in Vietnam, 2 in Cambodia) were identified by investigations of household contacts of index A(H5N1) case patients.

Conclusions and Relevance Asymptomatic human infections with A(H5N1) virus have been infrequently reported, with most cases identified through enhanced surveillance or household contact investigations of persons with known exposure. Robust data collection is needed from persons with possible asymptomatic A(H5N1) virus infection to inform future public health responses.