Interactions of the CO molecule with the Cu+ sites within MFI and FER matrices were investigated by means of the combined quantum mechanics/interatomic potential function method. CO molecules strongly interact with both dominant Cu+ site types (on the channel wall and on the channel intersection) in high-silica zeolite matrices. Upon interaction with CO, the Cu+ ion stays coordinated to only two oxygen atoms of the single AIO(4) unit. The structure, coordination, and CO stretching frequencies were found to be very similar for both Cu+ site types. On the contrary, adsorption energies differ for individual site types. The results are in agreement with the available experimental data, and they were confirmed by the TPD experiments carried out for various zeolite matrices.