In recent years, the avian influenza virus has emerged as a significant threat to both human and public health. Despite this, only two cases of human infection with the H10N3 strain have been documented. Here, we present the initial instance of human infection with avian influenza virus H10N3 in Yunnan Province, Southwest China. The patient, a previously healthy 51-year-old male, presented with recurrent fever peaking at 39℃, accompanied by symptoms such as cough, expectoration, chest tightness, and shortness of breath. Diagnosis revealed severe pneumonia, type I respiratory failure, and infection with avian influenza virus H10N3. Additionally, the patient experienced complications from Candida albicans and Staphylococcus epidermidis infections. Following treatment with appropriate antiviral drugs and antibiotics, the patient´s condition improved. Molecular analysis of the viral strain identified four mutations potentially hazardous to human health. This underscores the importance of continuous and vigilant monitoring of the dynamics surrounding the H10N3 subtype of avian influenza virus.