Grouper (Epinephelus malabaricus) were exposed to dietary copper at concentrations of 0, 5, 13, 24, or 41 mg/kg diet for six weeks, and changes in growth performance, RNA:DNA ratio, digestive enzyme activity, and oxidative stress were evaluated. Weight gain and specific growth rates increased and the feed conversion rate decreased as the dietary Cu concentration increased. The RNA:DNA ratio in the white muscle increased with the Cu concentration but the hepatosomatic and viscerosomatic indices were not affected (p>0.05). The protein efficiency ratio and condition factor were stimulated in a Cu concentration-dependent manner. Supplemental Cu produced an initial rise in digestive enzyme activity in the pyloric cecum and stomach, with the greatest stimulation occurring in fish fed the diet containing 13 mg Cu. Beyond this amount, however, activity decreased. Dietary Cu was positively related to Cu-Zn superoxide dismutase activity (SOD) at low concentrations and negatively related at high concentrations. The malondialdehyde level was inversely affected. In conclusion, RNA:DNA can be used as a biomarker to evaluate growth in grouper exposed to dietary Cu while changes in digestive enzyme activity and SOD were inconsistent with the Cu-induced variations in growth.