Doubly promoted MeMo/Nb2O5 catalysts, in which Me = Pt, Ni, or Co oxides were prepared for the selective catalytic reduction of NOx by CO reaction (CO-SCR). Comparable chemical, textural, and structural analyses revealed similarities between NiMo and CoMo impregnated on Nb2O5, in contrast to PtMo sites, which were not homogeneously dispersed on the support surface. Both the acid function and metal dispersion gave a synergistic effect for CO-SCR at moderate temperatures. The reactivity of PtMo catalysts towards NOx and CO chemisorption was at low reaction temperatures, whereas the NOx conversion over CoMo was greatly improved at relatively high temperatures. Careful XPS, NH3-TPD, and HRTEM analyses confirmed that the large amounts of strong and moderate acid sites from PtOx entrapped on MoO3 sites induced high NOx conversions. NiMo/Nb2O5 showed poor performance in all conditions. Poisoning of the MeMo sites with water vapor or SO2 (or both) provoked the decline of the NOx conversions over NiMo and PtMo sites, whereas the structure of CoMo ones remained very active with a maximum NOx conversion of 70% at 350 °C for 24 h of reaction. This was due to the interaction of the Co3+/Co2+ and Mo6+ actives sites and the weak strength Lewis acid Nb5+ ones, as well.