Heavy metal pollution can affect the immune capability of organisms. We evaluated the effect of cadmium (Cd) on the defense responses of the Pacifi c oyster Crassostrea gigas to Listonella anguillarum challenge. The activities of several important defensive enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), acid phosphatase (ACP), Na + , K + -ATPase in gills and hepatopancreas, and phenoloxidase-like (POL) enzyme in hemolymph were assayed. In addition, the expression levels of several genes, including heat shock protein 90 (HSP90), metallothionein (MT), and bactericidal/permeability increasing (BPI) protein were quantifi ed by fl uorescent quantitative PCR. The enzyme activities of SOD, ACP, POL, and GPx in hepatopancreas, and the expression of HSP90 were down-regulated, whereas GPx activity in the gill, Na + , K + -ATPase activities in both tissues, and MT expression was increased in Cdexposed oysters post L . anguillarum challenge. However, BPI expression was not signifi cantly altered by co-stress of L . anguillarum infection and cadmium exposure. Our results suggest that cadmium exposure alters the oysters' immune responses and energy metabolism following vibrio infection.