In the presence of CO2, copper degradation can proceed even if the applied electrochemical potential is not sufficient to drive CO2 ER. When CO2 is present in solution, copper and CO2-containing species form soluble complexes. Copper degradation does not happen if KHCO3 is present in solution without CO2. Ab initio calculations show that surface copper species are prone to dissolution under modest reducing potentials in the presence of CO2, most likely due to OCHO-containing complexes. Both our calculations and experimental measurements identify that Cu dissolution is exacerbated for oxidized surfaces that can lead to the formation of a larger number of soluble Cu complexes in the presence of CO2. Copper degradation is disfavored at more negative electrochemical potentials, where a strong electrochemical driving force opposes the dissolution process. The enhanced propensity of larger copper particles to degrade is rationalized with exacerbated pH changes that facilitate the formation of additional soluble copper complexes according to the DFT calculations.