In fish, environmental pollution is one factor that induces oxidative stress and this can disturb the natural antioxidant defence system. Oxidative stress has been well characterized in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied. In 2 experiments, we examined the impacts of copper (Cu) on gene expression, oxidative damage, and cell oxidative capacity in liver and gill of zebrafish. In the first experiment, soft-water acclimated zebrafish were exposed to 8 & 15 µg/L Cu for 48 h. This exposure resulted in significant increases in gene expression of cytochrome c oxidase 17 (COX 17) and catalase (CAT), associated with both increased Cu load and protein carbonyl concentrations in the gill and liver after 48 h. In addition, we examined the potential protective effects of increased waterborne Ca²⁺ (3.3mM) and Na⁺ (10mM) on acute Cu toxicity. While both treatments were effective at reducing liver and/or gill Cu loads and attenuating oxidative damage at 48 h, 10 mM Na⁺ was more protective than 3.3 mM Ca²⁺. There were variable changes in the maximal activities of cytochrome c oxidase (COX) and citrate synthase (CS), indicating possible alterations in cell oxidative capacity. Moreover, Cu affected COX/CS ratios in both gill and liver suggesting that Cu alters normal mitochondrial biogenic processes possibly though metallochaperones like COX 17. Overall, this study provides important steps in determining the transcriptional and physiological endpoints of acute Cu toxicity in a model tropical species.