The interaction between Mn and Cu ions is studied by measuring the resistance and electron paramagnetic resonance (EPR) at different temperatures of the Cu-doped compound La2/3Ca1/3Mn1−xCuxOy. A new transition inR-T curve and substantial enhancement in magnetoresistance are induced by the substitution of Mn ions by Cu ions. The EPR measurement shows that two resonance signals appear at temperature lower than the spin-ordering temperature of Mn ions. A tentative interpretation for the observed phenomena is proposed by considering the interaction between the Cu/Mn ions besides the Mn3+/Mn4+ ions.