Juvenile rainbow trout (Oncorhynchus mykiss) maintained on either low sodium chloride (LS (control), 1.4% NaCl) or high sodium chloride (HS, 11% NaCl) diet were exposed to 55 µg·L–1waterborne copper (Cu) for 28 days. Cu-exposed fish maintained on the LS diet exhibited 26% mortality, more than double (11%) that in fish maintained on the HS diet. Waterborne Cu exposure inhibited growth by 56% in fish maintained on the LS diet and by 35% in those maintained on the HS diet. Whole-body and tissue Na+levels, measured 6 h after feeding, were increased by exposure to HS diet and reduced by waterborne Cu exposure. Exposure to elevated waterborne Cu increased whole-body and tissue Cu levels, whereas exposure to HS diet decreased these levels. Moreover, whole-body and tissue Cu concentrations were consistently lower in Cu-exposed fish maintained on HS diet relative to those maintained on LS diet. Plasma Na+and Cl–levels were elevated by HS diet exposure and reduced by waterborne Cu exposure, whereas plasma Cu levels were decreased and increased by exposure to HS diet and waterborne Cu, respectively. These results demonstrate that elevated dietary NaCl modulates Na+and Cl–homeostasis and reduces accumulation and toxicity of waterborne Cu.