The goal of this study was to understand the structure-activity relationship for unpromoted and ceria-promoted MnOx/SiO2 catalysts used in CO oxidation. SiO2 and CeO2-promoted SiO2 (20% CeO2) were used as supports to prepare MnOx/SiO2 catalysts with various manganese (Mn) loadings. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) data indicated a higher Mn dispersion on ceria-promoted than on unpromoted MnOx/SiO2 catalysts. Analysis of the XRD patterns and Mn-2p XPS spectra indicated that Mn was present as MnO2 on MnOx/SiO2 with low Mn loadings and ceria-promoted MnOx/SiO2 catalysts and as mixed MnO2/Mn2O3 on MnOx/SiO2 catalysts with high Mn loadings. Kinetic data obtained for CO oxidation on unpromoted and ceria-promoted MnOx/SiO2 catalysts are presented and interpreted in correlation with the catalyst surface and bulk structure. A synergistic catalytic effect was observed in the case of the ceria-promoted MnOx/SiO2 catalysts. Post-reaction XRD and XPS analysis of catalysts indicated that the presence of ceria precludes formation of the less catalytically active Mn3O4 species from MnO2 deposited initially on the SiO2 support.