We report here an investigation on the preferential oxidation of carbon monoxide in an H2-rich stream (CO-PROX reaction) over mono and bimetallic Au-Ag samples supported on macro-mesoporous CeO2. The highly porous structure of ceria and the synergistic effect, which occurs between the bimetallic Au-Ag system and the support, led to promising catalytic performance at low temperature (CO2 yield of 88% and CO2 selectivity of 100% at 60 °C), which is suitable for a possible application in the polymer electrolyte membrane fuel cell (PEMFC). The morphological, structural, textural and surface features of the catalysts were determined by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), N2-adsoprtion-desorption measurements, Temperature Programmed Reduction in hydrogen (H2-TPR), Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS). Furthermore, the catalytic stability of the best active catalyst, i.e., the AuAg/CeO2 sample, was evaluated also in the presence of water vapor and carbon dioxide in the gas stream. The excellent performances of the bimetallic sample, favored by the peculiar porosity of the macro-mesoporous CeO2, are promising for possible scale-up applications in the H2 purification for PEM fuel cells.