African swine fever (ASF) is a highly infectious disease in pigs caused by the African swine fever virus (ASFV), which might result in 100% mortality. Pigs infected with ASFV might display different clinical and pathological features depending on virulence and host factors. This study aimed to determine features of clinical symptoms, macroscopic, and microscopic lesions of ASF in the Mekong Delta (MD), Vietnam during 2021–2022. The investigation was conducted following three fatal outbreaks of ASF in Hau Giang, Vinh Long, and Can Tho provinces, which are three central provinces out of thirteen in the MD. The spleen, lymph nodes, liver, kidney, and heart were collected from three infected pigs that displayed clinical symptoms of ASFV infection and confirmed the presence of ASFV by conventional PCR. The results indicated that infected pigs showed common clinical symptoms including high fever, anorexia, and moderate petechiae on the skin. Severe hemorrhage was observed in lymph nodes, spleen, kidneys, intestines, and gallbladders which were the main lesions during post-mortem examination. Microscopic lesions were characterized by lymphocytopenia, atrophy of lymphoid follicles in the immune system. However, distinct variations in clinical symptoms, macroscopic, and microscopic features among ASFV infection cases were not documented. This study provides a further understanding of the clinical presentation and
pathological lesions caused by the ASFV strain circulating in the MD