Ostwald ripening is a key mechanism for sintering of highly dispersed metal nanoparticles in supported catalysts. However, our microscopic understanding of such processes is still primitive. In this work, the atomistic mechanism of the Ostwald ripening of Cu on CeO2(111) is examined via density functional theory calculations. In particular, the detachment of a single Cu atom from ceria supported Cun (n = 2-10, 12, 14, 16, 18, and 20) clusters and trapping on the CeO2(111) surface is investigated in the absence and presence of CO adsorption. It is shown that the adsorption of CO on Cu reduces its detachment energy, which helps in the formation of single atom species on CeO2(111). In addition, the Cu1-CO species is found to diffuse on the CeO2(111) surface with a much lower barrier than a Cu atom. These observations suggest an efficient mechanism for the Ostwald ripening of Cu clusters supported on ceria in the presence of CO. It is further predicted that the Cu1-CO species can eventually migrate to a step site on ceria, generating a stable single-atom motif with a relatively larger binding energy. Finally, the single Cu atom catalyst is shown to possess high activity for the oxygen reduction reaction.