Abstract Copper is an essential and toxic trace metal that can adversely affect metal-requiring enzymes and proteins, and cause oxidative damage. Oysters, Crassostrea virginica, bioconcentrate Cu from environments contaminated by a variety of point and non-point sources. The purpose of these studies was to evaluate a suite of cellular parameters (lysosomal destabilization, glutathione concentrations, lipid peroxidation, and metallothioneins) in Cu-exposed oysters (5 to 80 μgl −1 for two weeks) in order to distinguish between exposure and stress responses. Copper exposures caused increased lysosomal destabilization, increased lipid peroxidation, and induction of Cu metallothioneins, but no effects on glutathione were observed. Experiments were also conducted in which BSO was used to deplete glutathione to consider how other environmental factors that affect amelioration responses may potentiate Cu toxicity. Lysosomal destabilization rates were significantly higher in glutathione-depleted oysters. Lipid peroxidation was higher initially during the first four days of Cu exposures, but then the levels declined to control levels. This amelioration was associated with the increased expression of metallothioneins. During the first four days of Cu exposure, no significant increases in MTs were observed, but subsequent induction of MTs was associated with reduced lipid peroxidation. Some cellular responses to Cu exposures represent normal compensatory mechanisms that may effectively ameliorate the insult. Therefore, it is important to appreciate the significance of the response or use a suite of responses to determine when effects have progressed from an exposure response to really being a signal of stress.