ABSTRACT Zinc pyrithione (ZnPT) is one of the components used in antifouling paints and can be an alternative to classical toxic chemicals such as organotin. However, there is still remarkable concern about the environmental safeness of ZnPT due to rapid transchelation and degradation into several metabolites that have their own toxicity. The effect after acute exposure of ZnPT is investigated on Mediterranean mussels exposed to 20 and 40 μg/L concentrations for 48 and 96 h and antioxidant responses [superoxide dismutase (SOD), and reduced glutathione (GSH)], genotoxicity [micronuclei (MN) frequency], apoptotic and histological changes were determined. Severe histological changes in hepatopancreas and gill tissues of mussels were observed in ZnPT exposed groups due to dose-dependent increase. ZnPT also caused a dose-dependent increase of TUNEL-positive cell count in the mussel tissues, especially in the hepatopancreas. Increasing in SOD activities and decreasing in GSH levels in both ZnPT concentrations compared to the control were observed. MN and binuclei numbers in all exposure groups were significantly increased. The results of the present study demonstrate that acute exposure to ZnPT could cause an adverse effect on mussel tissues at especially higher concentrations.