The interaction of CO with the bare TiC(001) surface and with Aun (n = 4, 9, 13) nanoparticles supported on the same TiC(001) surface has been studied by means of periodic density functional theory (DFT) based calculations with large supercell slab models. CO adsorption on the bare TiC(001) surface involves the direct interaction with a C surface atom and leads to a significant deformation of the underlying substrate. Because of this feature the calculated adsorption energy significantly varies with coverage. A comparison with available experimental data shows that this system is more complex than expected. The interaction of CO with the Au nanoparticles involves preferential bonding to low coordinated Au atoms. However, although the supported Au nanoparticles bind CO well, the adsorption energy of the molecule on the admetal is somewhat smaller than the one corresponding to the naked carbide surface and decreases with increasing the particle size, which is also consistent with a rather small red shift of the vibrational frequency of the adsorbed CO molecule that also decreased with increasing particle size. Implications for the use of Au/TiC systems in catalytic reactions involving CO are also discussed.