Mixed silver-copper oxide Ag2Cu2O3 was investigated by a combination of physicochemical techniques, including X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and temperature programmed reaction (TPR). The catalytic properties of Ag2Cu2O3 in the reaction of CO oxidation were studied by the TPR-CO + O2 method and compared with those of CuO nanopowder characterized by a similar specific surface area. On the surface of Ag2Cu2O3, two unequivalent oxygen species (Eb(O1s) = 529.4 eV and 531 eV) with different reaction probability towards CO were observed. Previously, similar oxygen species had been found on the surface of CuO nanopowder. Mixed silver-copper oxide interacted with CO at room temperature, which resulted in the surface reduction Cu2+ → Cu1+. Such reduction was accompanied by the removal of only oxygen with Eb(O1s) ∼ 531 eV. When the mixed oxide was heated in the reaction medium, both oxygen species were eliminated from the surface, leading to the partial decomposition of the Ag2Cu2O3 structure and the appearance of metallic silver. The TPR-CO study showed the presence of weakly bound oxygen species which can be adsorbed on oxygen vacancies in the Ag2Cu2O3 paramelaconite structure. The energy of oxygen vacancy formation on the (001) and (101) surfaces of Ag2Cu2O3 were calculated by periodic density functional theory (DFT). The role of different oxygen species in CO oxidation over the Ag2Cu2O3 surface is discussed.