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Spotted sea bass (<i>Lateolabrax maculatus</i>) is a high-economic-value aquacultural fish widely distributed in the coastal and estuarine areas of East Asia. In August 2020, a sudden outbreak of disease accompanied by significant mortality was documented in <i>L. maculatus</i> reared in marine cage cultures located in Nanhuang island, Yantai, China. Two coinfected bacterial strains, namely, NH-LM1 and NH-LM2, were isolated from the diseased <i>L. maculatus</i> for the first time. Through phylogenetic tree analysis, biochemical characterization, and genomic investigation, the isolated bacterial strains were identified as <i>Vibrio harveyi</i> and <i>Photobacterium damselae</i> subsp. <i>piscicida</i>, respectively. The genomic analysis revealed that <i>V. harveyi</i> possesses two circular chromosomes and six plasmids, while <i>P. damselae</i> subsp. <i>piscicida</i> possesses two circular chromosomes and two plasmids. Furthermore, pathogenic genes analysis identified 587 and 484 genes in <i>V. harveyi</i> and <i>P. damselae</i> subsp. <i>piscicida</i>, respectively. Additionally, drug-sensitivity testing demonstrated both <i>V. harveyi</i> and <i>P. damselae</i> subsp. <i>piscicida</i> exhibited sensitivity to chloramphenicol, ciprofloxacin, ofloxacin, orfloxacin, minocycline, doxycycline, tetracycline, and ceftriaxone. Moreover, antibiotic resistance genes were detected in the plasmids of both strains. Extracellular product (ECP) analysis demonstrated that both <i>V. harveyi</i> and <i>P. damselae</i> subsp. <i>piscicida</i> can produce hemolysin and amylase, while <i>V. harveyi</i> additionally can produce caseinase and esterase. Furthermore, infected fish displayed severe histopathological alterations, including infiltration of lymphocytes, cellular degeneration and necrosis, and loose aggregation of cells. Artificial infection assays determined that the LD₅₀ of <i>P. damselae</i> subsp. <i>piscicida</i> was 3 × 10⁵ CFU/g, while the LD₅₀ of <i>V. harveyi</i> was too low to be accurately evaluated. Furthermore, the dual infection of <i>V. harveyi</i> and <i>P. damselae</i> subsp. <i>piscicida</i> elicits a more rapid and pronounced mortality rate compared to single challenge, thereby potentially exacerbating the severity of the disease through synergistic effects. Ultimately, our findings offer compelling evidence for the occurrence of coinfections involving <i>V. harveyi</i> and <i>P. damselae</i> subsp. <i>piscicida</i> in <i>L. maculatus</i>, thereby contributing to the advancement of diagnostic and preventative measures for the associated disease.