Reactive oxygen species (ROS) such as the free radicals (e.g. hydroxyl, nitric acid, superoxide) cause damage to lipids, proteins and DNA. Increased production of ROS occurs from pollution. Process of removal or neutralization of ROS is achieved through antioxidants enzyme defense systems and provide homeostasis within biological systems. Aerobic organisms have complex antioxidant systems using enzymatic and non-enzymatic antioxidants to prevent overproduction of ROS. This study examined the toxic effects of arsenic and zinc on Eastern oysters, their interaction and resulting enzymatic responses. Cellular damage as indicated with lipid peroxidation and antioxidant defensive enzyme activities (superoxide dismutase, SOD; glutathione peroxidase, GPX and catalase, CAT) were measured in the hepatopancreas of Eastern oysters exposed to single and combined treatments of arsenic and zinc for 30 days. The results showed either arsenic or zinc exposure significantly increased the lipid peroxidation and triggered antioxidant defenses. Activities of antioxidant enzymes (SOD, GPX and CAT) were markedly elevated upon expose of As or Zn. However, at the presence of Zn, As toxicity expressed as lipid oxidation significantly decreased as well as accordingly decreased activities of antioxidant enzymes. This revealed that the presence of Zn showed a significantly antagonistic effect on arsenic toxicity in Eastern oysters from Northern Gulf of Mexico.