The production of dimethyl ether (DME) as compared to methanol from synthesis gas allows for increased conversions in a single pass. A challenge in this process is the combination of methanol synthesis and dehydration functionalities in a single catalyst without mutual negative interference of their performances. Here, we studied the use of hydrated niobium pentoxide (Nb2O5.nH2O) and niobium phosphate (NbOPO4) in combination with a copper-based methanol synthesis catalyst in the direct synthesis of DME, while gamma-alumina (gamma-Al2O3) was used as a reference material. The three solid acids combined with the copper-based catalyst proved active and selective in the production of DME, however all of them showed some degree of deactivation throughout the reaction. Characterization of the used catalysts pointed out that while the gamma-Al2O3-based mixture deactivated most likely due to coke deposition on the alumina and structural changes in the methanol synthesis catalysts, the Nb2O5.nH2O and NbOPO4-based catalysts lost activity probably as a result of copper migration from the methanol synthesis catalyst to the acid component. In view of the high volume-based activity of the Nb-based solid acids it is concluded that these are promising components for the direct catalytic conversion of synthesis gas to DME.