In the study the effects of copper sulphate (CS) and rumen-protected copper sulphate (RPCS) addition on performance, nutrient digestibility, rumen fermentation and hepatic gene expression in bulls were evaluated. Thirty-six Holstein bulls were randomly assigned to three treatments: control (without Cu supplementation), CS (8 mg/kg dry matter (DM) Cu from CS) and RPCS (8 mg/kg DM Cu from RPCS). Dietary Cu addition did not affect DM intake and average daily gain, but increased apparent nutrients digestibility. Ruminal pH, propionate percentage and ammonia-N concentration decreased, but total volatile fatty acids concentration and acetate percentage increased with dietary Cu inclusion. Activities of carboxymethyl-cellulase, xylanase and laccase and populations of total bacteria, Butyrivibrio fibrisolvens and Ruminococcus albus increased, but α-amylase activity decreased with dietary Cu provision. In bulls receiving RPCS supplementation greater activities of xylanase, pectinase and α-amylase and populations of Ruminococcus flavefaciens and Butyrivibrio fibrisolvens were noted than in those receiving CS addition. Activities of laccase and protease were lower in RPCS group than in CS one. Liver Cu concentration was the highest in RPCS animals, followed by CS, and then control ones. Hepatic expressions of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, phosphoinositide 3-kinase and ribosomal protein S6 kinase were reduced by RPCS, but were not affected by CS addition. Hepatic expression of mammalian target of rapamycin was the lowest in RPCS group, followed by CS, and then control ones. It is suggested that dietary Cu addition promoted nutrients digestion and ruminal fermentation, and replacement of CS with RPCS down-regulated hepatic protein synthesis metabolism genes expression.