The tissues of marine invertebrates are colonized by species-rich microbial communities. The dysbiosis of host’s microbiota is tightly associated with the invertebrate diseases. Yesso scallop (Patinopecten yessoensis), one of the most important maricultured scallops in northern China, has recently suffered massive summer mortalities, which causes huge production losses. The knowledge about the interactions between the Yesso scallop and its microbiota is important to develop the strategy for the disease prevention and control. In the present study, the bacterial communities in hemolymph, intestine, mantle and adductor muscle were compared between the healthy and diseased Yesso scallop based on the high-throughput sequencing of 16S rRNA gene. The results indicated obvious difference of the composition rather than the diversity of the bacterial communities between the healthy and diseased Yesso scallop. Vibrio, Francisella and Photobacterium were found to overgrow and dominate in the mantle, adductor muscle and intestine of the diseased scallops, respectively. The prediction of bacterial community metagenomes and the variations of KEGG pathways revealed that the proportions of the pathways related with neurodegenerative diseases and carbohydrate metabolism both increased significantly in the mantle and hemolymph of the diseased scallops. The abundance of the metabolism pathways including carbohydrate metabolism, lipid metabolism and amino acid metabolism decreased significantly in the intestine of diseased scallops. The results suggested that the changes of bacterial communities might be closely associated with the Yesso scallop’s disease, which was helpful for further investigation of the pathogenesis as well as prevention and control of the disease in Yesso scallop.