Cu/ZnO catalysts with different mean Cu particle sizes were prepared by wet impregnation of copper nitrate onto a zinc oxide support. Their performance was studied in methanol synthesis reaction from CO₂ and H₂ at temperatures between 160 and 225 °C and a pressure of 7 bar. Selective methanol formation is favored at lower temperatures due to the suppression of CO production. Activation energies were 8–11 kcal mol⁻¹ for methanol formation and 29–31 kcal mol⁻¹ for CO formation and were similar for all the catalysts. For catalysts with copper cluster sizes between 8.5 and 37.3 nm, the methanol formation rates normalized by surface copper atoms were independent of copper particle size. On the contrary, CO formation rates are enhanced over catalysts with smaller copper clusters. Higher selectivity to methanol is favored over catalysts possessing larger copper nanoparticles. Catalysts with copper loading ≥8 wt.% showed a strong sintering of copper nanoparticles and also a significant growth of ZnO support crystallites. These catalysts presented higher intrinsic rates for methanol formation (4 × 10⁻³ s⁻¹ at 180 °C) compared to catalysts with lower copper loading (0.9 × 10⁻³ s⁻¹). As the kinetic parameters were similar for all Cu/ZnO catalysts, it is proposed that catalysts with large copper and ZnO particles form new active sites that led ultimately to a very high methanol synthesis activity and selectivity. It is suggested that the important sintering of Cu particles modifies the structure of copper promoting the hydrogenation rate in methanol synthesis.