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A previous study confirmed that spotted sea bass (Lateolabrax maculatus), an economically important cultured species in East Asia, is a new host of Aeromonas veronii , which can cause acute death in these fish, but there is little in-depth understanding of this disease. In the present study, the virulence of 10 isolates of A. veronii derived from spotted sea bass was determined. It was found that the 18BJ181 isolate was a virulent strain and led to the fastest death of spotted sea bass. Death was determined to be within in 2–12 h, and resulted in abdominal effusion and varying degrees of hemorrhage in internal organs. Bacterial colonization analysis showed that the bacterial load in the spleen was highest, and was up to 3.1 × 105 cfu g−1. In addition, the bacteria proliferated massively in the blood and reached 2.4 × 107 cfu mL−1 at 12 h after 18BJ181 strain infection, which was also a typical feature of acute septicemia. Histopathology of the spleen revealed edema in interstitial tissue, degeneration, and necrosis in lymphoid tissue, and hemorrhage in the capillary network. Transcriptome analysis of the spleen showed that the expression level of HSP70 , CCL19 , and IL-1β was extremely significantly up-regulated at 8 h after infection (P < 0.01), and the expression of these genes was normal at 24 h. These results revealed that A. veronii infection could rapidly activate the chemokine signal pathway and stimulate the acute inflammatory response in the host. The bacterial colonization, pathological features, and gene expression patterns in immune pathways will help us to better understand acute septicemia in spotted sea bass caused by A. veronii. • Aeromonas veronii caused acute septicemia in spotted sea bass. • The target organ of A. veronii colonization was spleen. • A. veronii infection activate an inflammatory response in spotted sea bass. [ABSTRACT FROM AUTHOR]