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Chlorpyrifos (CPF) is an environmental pollutant with increasing importance due to its high toxicity to fish and aquatic animals. To understand how CPF impacts immune response and oxidative stress in common carp (Cyprinus carpio L.), we investigated the transcriptomic profiles of the head kidneys from common carp exposed to CPF for 15days. A total of 52, 297, 928 and 52, 273, 784 high quality clean reads were obtained from CPF exposure groups, 44,677,578 and 44,106,696 high quality clean reads were obtained from corresponding control groups. Among them, 456 genes were differentially expressed, including 246 up-regulated genes and 210 down-regulated genes identified and enriched in databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Antioxidant systems, and immune response genes and pathways were verified by quantitative real-time RT-PCR. We found that CPF-induced ROS regulates immune response by stimulating the antigen-presenting ability of head kidney in carp. These results provide new insights for unveiling the biological effects of CPF in common carp.First time to perform a deep transcriptome analysis in common carp by chlorpyrifos exposed.Chlorpyrifos could induce oxidative stress in head kidney of common carp.Chlorpyrifos could increase MHC class II molecules in head kidney of common carp.