The behavior of a series of palladium catalysts supported on alumina, ceria, and ceria/alumina for the CO+O 2 reaction has been analyzed by a combination of electron transmission microscopy, infrared and electron paramagnetic resonance spectroscopies, and catalytic test studies. Ceria is shown to decrease the onset of the reaction by ca. 130 K due to an enhanced activation of both reactant molecules. Even at room temperature, ceria facilitates activation of CO by promoting the formation of metallic palladium and that of oxygen by the presence of reactive vacancies at the Pd–Ce interface. The optimum ceria promoting effect in the CO conversion is observed for palladium particles in contact with 3-dimensional ceria supported particles, which seem to be oriented by their interaction with alumina, and ascribed to the specific characteristics of the anionic vacancies located at the corresponding Pd–Ce interface. The bulk ceria support, however, induces an oxidation–deactivation process of palladium at medium and high reaction temperatures which hinders reaction between Pd-bonded CO and Ce-bonded oxygen at the Pd–Ce interface.