CO-induced changes in the metal/metaloxide interaction of MgO(100)-supported palladium, silver, platinum, and gold in the form of atoms and layers have been investigated within the density functional theory. CO is found to modify the metal/MgO(100) interaction for atoms and one-atom-thick layers. Generally, the bond strength is enhanced, with the largest increase calculated for Pt (similar to1 eV). For metal atoms, CO adsorption is found to increase the barrier of diffusion. The underlying mechanism for bond strengthening is traced back to a matching between the CO-metal and metal-metaloxide bond characteristics. The effect of support-induced changes for an arbitrary adsorbate-metal interaction is predicted to be small beyond three atomic layers.