Oxide-derived Cu (OD-Cu) catalysts have shown an excellent ability to ensure C-C coupling in the electrochemical carbon dioxide reduction reaction (eCO2RR). However, these materials extensively rearrange under reaction conditions, thus the nature of the active site remains controversial. Here, we studied the reduction process of OD-Cu via large-scale molecular dynamics at first-principles accuracy introducing experimental conditions. The oxygen concentration in the most stable OD-Cu materials increases with the increase of the pH/potential/specific surface area. In long electrochemical experiments, the catalyst would be fully reduced to Cu, but it takes a considerable amount of time to remove all the trapped oxygen, and the highly reconstructed Cu surface provides various sites to adsorb oxygen under relatively stronger reduction potentials (U = –0.58 VSHE at pH=14, 0.25 VRHE). This work provides insight into the evolution of OD-Cu catalysts and residual oxygen during the reaction conditions and a deep understanding of the nature of active sites.