In this work, we show that CO2 plays a primary role in the degradation of copper during the CO2 ER. We conduct systematic investigations of the various microenvironment factors contributing to copper degradation towards decoupling the electrolyte composition, the solution pH, the applied electrochemical potential, and the presence/absence of CO2. Based on in situ experimental observations and firstprinciples calculations, we propose that the oxidized and unoxidized surface copper atoms can form complexes with CO2 depending on the electrode potential. This causes corrosion, preferentially along lower-coordinated surface sites. These results provide insights needed to inhibit copper corrosion and develop highly stable copper-based catalysts that can withstand longer operational times for CO2 ER or other electrochemical reactions.