Abstract: In order to investigate the immune response mechanism of large yellow croaker (Larimichthys crocea) against Vibrio alginolyticus infection, the transcriptome changes in head kidney 24h after infection were analyzed by high-throughput sequencing and bioinformatic analysis. A total of 1903 differentially expressed genes (DEGs) were obtained, of which 641 were up-regulated and 1262 were down-regulated. After Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, the results showed that some innate immune-related genes, including complement (C1qbp, C1QL2 and C7), heat shock protein (hspd1, hspa4, hspa5 and hspa9), antimicrobial peptide (Hepcidin-1), C-type lectin receptor (Clec4e and MR1), hexokinase (hex1), arginase (Arg-II), and Tu translation elongation factor (TUFM) were significantly up-regulated. While many adaptive immune-related genes, including T and B cell proliferation and differentiation (FcR5 and CCL17), T cell regulatory factors (TCRα, TCRβ, CD3ε, CD3γδ, CD3ζ, ZAP-70 and ITK), and antigen recognition factors of Immunoglobulin (Ighv 5A, Ighv 914 and Ighv XIG14) were significantly down-regulated. Besides, GO terms related to aerobic metabolism, like Hemoglobin complex, Oxygen binding and Oxygen carrier activity also got significant enrichment, of which all DEGs were down-regulated in infection group. The results indicated that in the early stage of V. alginolyticus infection, the innate immunity of large yellow croaker was activated, while the adaptive immunity was inhibited. Since the late activation of adaptive immunity, in early stage of bacterial infection, the blocking of TCR signal pathway, and the inhibition of proliferation and differentiation of specific immonocytes might save enough energy for innate immunity, which was beneficial to the immune response of fish against bacterial infection. Our results also showed that after V. alginolyticus infection, oxygen transfer ability of large yellow croaker was decreased, which might be related to the hemolytic activity of the bacterium.