The current study evaluated appetite-related gene expression of neuropeptide Y (NPY), orexin, type 2 orexin receptor (OrexinR2), proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R), AMP-activated protein kinase α2 subunit (AMPKα2) and long-form leptin receptor (LeptinRb) in hypothalamus in response to copper (Cu) supplementation. One hundred crossbred pigs were assigned to four groups of 25 pigs, each comprising five replicates of 5 animals. Groups were then randomly assigned to treatments consisted of 1. control (10 mg/kg CuSO₄), 2. 100 mg/kg CuSO₄, 3. 175 mg/kg CuSO₄, 4. 250 mg/kg CuSO₄. On d 21 of the experiment 5 pigs from each group were slaughtered and the hypothalami were collected for determination of appetite-regulating genes mRNA expression level. The results showed that average daily feed intake and average daily gain were higher (P<0.05) in 250 and 175, 250 mg/kg Cu supplemented groups, respectively, than in the 10 mg/kg group. Feed:gain ratio was lower in pigs fed the diets with 250 mg/kg Cu (P<0.05) than in the 10 mg/kg group. Furthermore, the abundances of NPY mRNA in hypothalamus were higher in 250 mg/kg Cu supplemented groups (P<0.05), whereas the abundances of POMC and LeptinRb mRNA were significantly reduced (P<0.05) in 170, 250 mg/kg and 100, 175, 250 mg/kg Cu supplemented groups, respectively. No difference was found for AMPKα2, MC4R, orexin, OrexinR2 mRNA expression (P>0.05). These data suggest that down-regulation of LeptinRb mRNA expression might contribute to the stimulation of feeding of high dietary Cu supplementation via regulation of NPY and POMC mRNA expression.