The aim of this study was to evaluate whether zinc (Zn) supplementation protects against hepatic copper (Cu) accumulation in copper-loaded sheep. Forty cross-bred lambs were assigned to five experimental groups. These included the control group (C) and four treatment groups that received Cu and/or Zn supplementation (dry matter (DM) basis) over 14 weeks, as follows: Cu (450 mg Cu/kg); Zn-35 (450 mg Cu + 35 mg Zn/kg); Zn-150 (450 mg Cu + 150 mg Zn/kg); and Zn-300 (450 mg Cu + 300 mg Zn/kg). Blood, liver, and bile samples were obtained for mineral determination by inductively coupled plasma optical emission spectrometry (ICP–OES). The hepatic metallothionein (MT) concentrations were also determined. At the end of the experiment, hepatic Cu concentrations were higher in all Cu-supplemented groups than in C. Hepatic Cu accumulation was lower in the groups receiving the Zn supplementation than in the Cu group, although the difference was only statistically significant (66%) in the Zn-300 group. The MT concentrations tended to be higher (almost two-fold) in the Zn groups (but were not dose related) than in the C and Cu groups, and they were related to hepatic Zn concentrations. Zn supplementation at 300 mg/kg DM is useful for preventing excessive hepatic Cu accumulation in sheep exposed to high dietary concentrations of Cu.