The impact of diffusion in porous catalyst pellets on the methanation of CO/CO2 mixtures was successfully investigated by physical experiments and numerical simulations at different temperatures. By adjusting one single parameter (the tortuosity 𝜏) only, experiment and simulation agree well with respect to the effective methane formation rate, which underpins the validity of the reaction kinetics and the diffusion model used in the simulations. The analysis of the simulation results reveals significant differences in the spatial profiles of molar fractions of CO and CO2 in the solid catalyst, even though the diffusion coefficients are similar. In particular, the inhibiting effect of CO on both hydrogenation of CO and CO2, expressed by the reaction kinetics, induces different reaction regimes depending on the extent of diffusion limitations. For low diffusion limitations, a slightly positive effect on the effective methane formation rate is observed for small CO/CO2 ratios. For severe diffusion limitations, even a shift in reactant selectivity towards hydrogenation of CO2 is observed, which allows to achieve a significant conversion in CO2 even though CO is present to a high extent at the reactor inlet, as well. Hence, the appropriate design of the pellet size is an important parameter for the reactant selectivity during methanation of CO/CO2 mixtures. Importantly, hydrogenation of CO is always favored over CO2, irrespective of the degree of diffusion limitations, since CO is preferable adsorbed at the active site. Because this not only holds for Ni-based catalysts investigated in the present work, the principle trends are probably also transferable to other active metals for methanation, such as ruthenium, cobalt or iron. However, this presumption requires validation by experiments and simulations in future work, as demonstrated in principle in the present work.