Several CeO₂-CuO/Cu₂O nanocomposites with different CuO structures were used to identify the structure sensitivity of CuO in the CeO₂-CuO/Cu₂O catalyzed CO oxidation. The CO oxidation catalyzed by various CuO-CeO₂ interfacial sites involves a typical Mars-van Krevelen mechanism, in which the CuO-CeO₂ interfaces in the CeO₂-CuO/c-Cu₂O (cubes) nanocomposites are more intrinsically active, exhibiting ca. 15 kJ mol⁻¹ lower activation energy than those in the CeO₂-CuO/o-Cu₂O (octahedra) and CeO₂-CuO/d-Cu₂O (rhombic dodecahedra) nanocomposites at CeO₂ loadings no less than 0.75 wt%. The higher activity is relevant to lower coordinated oxygen ions on CuO/c-Cu₂O surface and thus better CO reactivity for the CeO₂-CuO/c-Cu₂O nanocomposites, which therefore indicates that the active oxygen species on CuO-CeO₂ interface should come from CuO rather than CeO₂. Moreover, a highly active 13.2 %CeO₂-CuO/c-Cu₂O(s) catalyst for CO oxidation is realized on fine Cu₂O cubes, which thus has high density of active sites.