In this work, the behavior of a novel manganese-promoted inverse CeO2/CuO catalyst under water-gas shift (WGS) reaction conditions is studied. CeO2/CuO and CeO2/Mn-CuO catalysts are characterized by X-ray diffraction (XRD), Raman and X-ray photoelectron spectroscopy (XPS). Structure/activity relationships and redox characteristics are established on the basis of such results along with those of in situ XRD and X-ray absorption fine structure (XAFS) experiments performed either under WGS or CO-temperature programmed reduction (TPR) conditions. The manganese coprecipitated together with the copper during the preparation of the samples and the Mn-CuO phase strongly affected the size and chemical properties of the catalytically-active ceria nanoparticles. A manganese-induced enhancement on the WGS activity was observed. Differences in the characteristics of the supported ceria particles are proposed as most relevant to explain the observed Mn-promoting effect.