Magnesia-supported highly-dispersed CuO solids were prepared by impregnation and mechanical mixing of CuO nanopowders with MgO. Additionally, ultrasound and mechanochemical treatment of CuO nanopowders mixed with MgO was performed. TEM and XRD studies indicate that the size of the CuO nanoparticles in solids depends on the method of preparation. Catalytic tests of these solids in the CO oxidation show that varying the method of catalyst preparation changes the temperature of the 100% conversion CO by more than 130 degrees C. Fabrication of the CuO-MgO catalysts via an easy mixing process using CuO nanopowder and cubic MgO gives the most active catalyst. Mechanochemical and/or ultrasound treatments lead to catalyst deactivation. Our results show that method of the catalyst preparation influences the catalyst performance mainly through varying the CuO nanoparticle size and CuO-support interaction.