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.