Despite the importance of CO adsorption in many electrocatalytic reaction mechanisms, there has been little investigation of the dependence of the free energy of CO adsorption on the applied potential. Herein, we report on the potential-dependent adsorption of CO on Cu electrodes using a grand-canonical density functional theory approach. We demonstrate that, within the working potential range of electrocatalytic CO2 reduction on Cu(111) and Cu(100), the CO adsorption strength can change by over 0.1 eV. Our analyses explain the potential dependence through an interfacial capacitance loss upon CO adsorption as well as orbital relaxation induced by the electrode potential. Via sensitivity analysis with respect to two electrolyte model parameters (solvent dielectric constant and Debye screening length), we find that the surface excess charge density is a useful descriptor of the CO adsorption free energy.