In the present study, a potential pathogenic bacterium was isolated and identified from Pacific oysters (Crassostrea gigas) with abscess disease collected from a culture area in Zhuanghe, Dalian, Liaoning. Exiguobacterium profundum was identified in the lesions of the diseased C. gigas using 16S rDNA sequencing and bioinformatics techniques. Antimicrobial susceptibility and hemolysis experiments were conducted. The expression of inflammation-related genes and changes in bacterial community structure in the gill tissues following E. profundum infection were further analyzed using artificial infection experiments, high-throughput sequencing technology, and quantitative real-time PCR. The results showed that the strain formed creamy-yellow colonies with a diameter of 1.0-1.5 mm on marine agar 2216 E, exhibiting uniform and stable morphology. E. profundum demonstrated high sensitivity to cefoperazone, penicillin, and amoxicillin. It exhibited significant β-hemolytic activity at 28 °C. Artificial infection experiments revealed the presence of abscesses on the mantle and white spots and swelling on the gills, with significant increases in the mRNA expression levels of Cgtlr3, Cgap-1, Cgcaspase-3, Cgil-17-5 and Cgil-17-6 in the gills post-infection. High-throughput sequencing analysis showed an increase in the relative abundance of Proteobacteria and Campylobacterota, as well as an induction in the relative abundance of Vibrionaceae in the gill tissues following E. profundum infection. These findings suggest that E. profundum may contribute to the pathogenesis of C. gigas by promoting the mRNA expression of inflammation-related genes and inducing the abundance of Vibrio spp. in the gill tissue. This study identifies E. profundum as a potential pathogen of C. gigas with abscess disease, providing valuable data support for the prevention and control of shellfish diseases.