The CO2 production by shift reaction and the deactivation process are the drawbacks of the One-Step DME Synthesis. Therefore, this contribution discusses possible deactivation modes taking into account the catalytic performance and the characterization of spent catalysts using XRD, TG and FTIR techniques. For this purpose a physical mixture that contains a commercial methanol catalyst and ZSM-5 was employed. It can be suggested that one of the main modes of catalyst deactivation is the hydrocarbon formation by MTG reactions. Changes in the interaction between Cu-0 and ZnO should also be considered. The results show that both of them are affected by H-2/CO ratio.