A study was conducted evaluating the effect of long-term Cu deficiency, with or without high Mn, on growth, gene expression and Cu status of beef cattle. Twenty-one Angus calves were born to cows receiving one of the following treatments: (1) 10 mg supplemental Cu/kg DM (+Cu); (2) no supplemental Cu and 2 mg Mo/kg DM ( − Cu); (3) − Cu diet plus 500 mg supplemental Mn/kg DM ( − Cu+Mn). Calves were weaned at approximately 183 d of age and individually fed throughout the growing and finishing phases. Plasma Cu was lower (P < 0·01) in − Cu calves compared with +Cu calves while high dietary Mn further depressed (P < 0·01) plasma Cu in − Cu+Mn calves v. − Cu calves. Liver Cu concentrations in +Cu calves were greater (P < 0·01) than in − Cu calves, with no differences between − Cu and − Cu+Mn calves. The daily body-weight gain of +Cu calves was greater (P < 0·01) than − Cu calves during the period from birth to weaning, but did not differ during the growing phase. − Cu+Mn calves gained less (P < 0·05) than − Cu calves during the growing phase. DM intake was lower (P < 0·01) in − Cu+Mn calves v. − Cu calves, and did not differ among +Cu and − Cu calves. The relative gene expression of cytochrome c oxidase in the liver was lower (P < 0·05) in − Cu calves compared with +Cu or − Cu+Mn calves. In conclusion, feeding a Cu − deficient diet in combination with high Mn negatively affected the growth and Cu status of beef cattle.