The kinetics of dimethyl oxalate (DMO) hydrogenation over Cu(111) and Cu2O(111) has been studied to understand the role of Cu-0 and Cu+ sites in ethyl glycol (EG) production over Cu-based catalysts by the combination of density functional theory calculations and microkinetic analysis. The calculated results suggest that the presence of the Cu+ sites would strengthen the binding of the reactants, products, and reaction intermediates to the substrate and thus promote the dissociation of DMO and H-2. The Cu-0 sites are found to be beneficial to the hydrogenation of the acyl species whereas the Cu+ sites are primarily responsible for the CH3OH formation. Microkinetic analysis indicates that the existence of the Cu+ sites would increase the turnover frequency for the EG formation on Cu(111) by a factor of 20, under typical operating conditions. Hence, the excellent catalytic performance of the Cu-based catalysts in the hydrogenation of DMO to EG is attributed to the synergistic effect between the Cu-0 and Cu+ sites, and a proper Cu-0/Cu+ molar ratio can dramatically improve the catalytic activity.