The catalytic conversion of ethanol was carried out over H3PMo12O40·xH2O (H3PMo) and its substituted copper ions with formula Cu0.5xH3−xPMo12O40 (where x = 1, 2 and 3). Pure and Cu-substituted catalyst samples were calcined at 350 ◦C. The effect of copper ions substitution on the thermal behaviour, structural, acidic, surface and catalytic properties of the investigated samples were studied using TG, DSC, FTIR, pyridine adsorption at 25 ◦C, N2 adsorption at −196 ◦C. Maximum selectivity of diethyl ether and the second major reaction product ethylene was obtained at 350 ◦C. The substitution of copper in the H3PMo resulted in increase of the selectivity towards diethyl formation to attain a maximum value using Cu2PMo-350 catalyst. Very high diethyl ether over ethylene yield values obtained in this study at 350 ◦C are highly promising for the production of petrochemicals from ethanol.