Fishes provide abundant protein for humanity, while they are ravaging by bacterial and viral diseases. The defense based on peripheral blood cell immunity is an important means to resist pathogenic infections. However, the immune response of different blood cell communities to bacterial or viral infection remains largely unknown. In this study, grass carp (Ctenopharyngodon idella), the most productive fish in the world, was employed to comprehensively investigate the immune responses of erythrocytes, leukocytes, and thrombocytes after Aeromonas hydrophila or type II grass carp reovirus (GCRV-II) infection by transcriptome sequencing. The data of 45 samples with small intra-group and large inter-group differences were obtained. There were 3921, 15,378, 7019 DEGs in the infected erythrocytes, leukocytes, and thrombocytes, respectively. Through GO and KEGG analysis, they were mainly enriched in the items related to innate and adaptive immunity, including pattern recognition receptor signaling pathways and cytokine signaling pathways. Therefore, we conducted target analyses of vital immune families, including TLRs, RLRs, IFNs, IRFs, immune activators, and antigen presentation genes, systematically clarified the immune responses of blood cells to pathogenic infections. All the three types of blood cells expressed a large number of immune genes involved in anti-infection to varying degrees, among them leukocytes and thrombocytes responded aggressively. This study provides implications for the function of peripheral blood cells and the functional basis of immune genes in pathogenic infections.