Background <p>Human infection with avian influenza A (H10N3) is a rare but severe emerging zoonotic disease. To date, only a limited number of cases have been reported, which restricts a comprehensive understanding of its clinical features and public health risks. We report the fourth documented case of human H10N3 infection, which is the first to be identified in a female patient. Additionally, we compared the clinical and genomic characteristics of all four cases.</p> Case presentation <p>A 23-year-old female with no prior comorbidities developed severe pneumonia and acute respiratory distress syndrome due to infection with avian influenza A (H10N3) virus. The patient, working in a fresh market with recent training at a slaughterhouse, presented a one-week history of high fever, cough, and dyspnea. Despite initial broad-spectrum antibiotics, her condition rapidly worsened, requiring mechanical ventilation and veno-venous extracorporeal membrane oxygenation (V-V ECMO). Metagenomic next-generation sequencing of bronchoalveolar lavage fluid, confirmed by the Centers for Disease Control and Prevention, identified avian influenza A (H10N3). Following approximately three months of intensive treatment, the patient recovered and was discharged. Phylogenetic analyses showed that her virus strain was closest to the third human H10N3 case (Kunming, China, 2024). In addition, this strain had a human-adapted substitution (P221) but lacked the G228S substitution in the haemagglutinin protein, suggesting that the latter is not essential for human infection.</p> Conclusions <p>This case highlights the potential for severe human infection by the H10N3 virus. It is imperative that surveillance is enhanced in both human and animal populations.</p>