Hypoxia often intensifies with rising dissolved CO2, but the concurrent effects of hypoxia and acidification on bivalves are largely unknown. In this study, immune responses of hemocytes in the mussel Mytilus coruscus were examined under six combinations of pH (7.3, 7.7 and 8.1) and dissolved oxygen (DO) concentrations (2 mg L− 1, 6 mg L− 1) for 72 h. Generally, total hemocyte account, phagocytosis, esterase and lysosomal content were reduced under low DO and pH conditions, whereas hemocyte mortality and reactive oxygen species production increased under low DO and pH. Both hypoxia and low pH have negative effects on mussels, but the effects of pH are not as strong as DO. Moreover, significant interactions between DO and pH occurred. However, acidification generally doesn't aggravate the effects induced by hypoxia. Acidification and hypoxia may increase disease risk and impact the aquaculture of this species.