Cadmium (Cd), a hazardous environmental contaminant with irreversible toxicity to fish, has been detected in aquatic environment of many countries. The common carp is one of the most widely distributed fish in the world, so we used common carp to assess environmental contaminant risk. In present study, we investigated effects of Cd on immune function, oxidative defense, and glycometabolism in the spleens of common carp by transcriptome analysis. Obtained 3794 differentially expressed genes (including 1848 up-regulated and 1946 down regulated genes) were enriched using databases of Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology in David bioinformatics software (version 6.8). The pathways and gene functions of immune, oxidative defense, and glycometabolism were obtained and identified. Some relative genes were validated using qRT-PCR and gene expression of IL-1 beta, INF-gamma, IL-6, Cxcl18b, HO-1a, CAT, GPx1, GCK, and FBA decreased; and gene expression of B4GALT1, GPAT3, and CYP26B1 increased. Our results indicated that Cd exposure led to immunosuppression, oxidative stress, and glycometabolism disorder in the common carp spleens. The present study gives a novel insight and method on environmental risk assessment.