The bacteriumAeromonas veroniiis a co-pathogenic species that can negatively impact the health of both humans and aquatic animals. In this study, we used single-cell transcriptome analysis (scRNA-seq) to investigate the effects of infection withA. veroniion head kidney cells and the regulation of gene expression in the dark sleeper (Odontobutis potamophila). scRNA-seq was used to assess the effects of infection withA. veroniiinO. potamophilaB cells, endothelial cells, macrophages, and granulocytes, and differential enrichment analysis of gene expression in B cells and granulocytes was performed. The analyses revealed a significant increase in neutrophils and decrease in eosinophils in granulocytes infected withA. veronii. Activation of neutrophils enhanced ribosome biogenesis by up-regulating the expression ofRPS12andRPL12to fight against invading pathogens. Crucial pro-inflammatory mediatorsIL1B, IGHV1-4, and the major histocompatibility class II genesMHC2AandMHC2DAB, which are involved in virulence processes, were upregulated, suggesting thatA. veroniiactivates an immune response that presents antigens and activates immunoglobulin receptors in B cells. These cellular immune responses triggered by infection withA. veroniienriched the available scRNA-seq data for teleosts, and these results are important for understanding the evolution of cellular immune defense and functional differentiation of head kidney cells.