Samaria-doped ceria (SDC) and SDC/gamma-alumina-supported copper catalysts were prepared by a co-impregnation method. Temperature-programmed reduction (TPR) analysis and X-ray diffraction were employed for catalyst characterization. The activities of CO oxidation over these catalysts were measured and compared. It was found that significant enhancement of catalytic activity was achieved for copper supported on SDC, leading to a precious metal-like catalytic behavior. Catalytic activity is governed by oxygen vacancies of SDC and interfacial active centers formed, not by the dispersion and BET surface area offered by gamma-Al2O3. Thus, SDC-supported Cu exhibits higher activity for CO oxidation than that of SDC/gamma-alumina-supported Cu. For Cu/SDC catalysts, the composition of samaria in SDC at which the maximum of CO oxidation activity occurs corresponds well with the maximum of the oc-peak area of TPR. The optimum CO activity is due to the maximum number of the interfacial active centers. The surface oxygen ions of the SDC and SDC/gamma-Al2O3 supports can be removed by hydrogen, which is associated with the reduction of ceria. These oxygen ions have been judged to be the surface capping oxygen ions, which coordinate beside the surface oxygen vacancies of SDC. The activity decline which resulted from excess samaria over the optimal composition of 5 mol% Sm2O3 in SDC can be attributed to the segregation of samaria.