Energetics of Ce–Zr substitution in xCe0.8Y0.2O1.9−(1−x)Zr0.8Y0.2O1.9 (0≤x≤1) solid solutions, potential candidates for electrolytes in solid oxide fuel cells, were investigated by high temperature oxide melt drop solution calorimetry. The enthalpies of formation relative to the solid solution end-members, Ce0.8Y0.2O1.9 and Zr0.8Y0.2O1.9 (ΔHf,ss), are slightly positive. The whole substitution range can be divided into three regimes: a zirconia-dominated region (0≤x<0.4), where ΔHf,ss increases from 0 to 3.9 kJ/mol; a ceria-dominated region (0.6<x≤1), where ΔHf,ss remains nearly constant at 0 to 0.7 kJ/mol; and a transitional region (0.4≤x≤0.6), where ΔHf,ss decreases from 3.9 to 0.7 kJ/mol. Such a trend in ΔHf,ss strongly supports a scavenging effect of Zr4+ on oxygen vacancies, i.e. oxygen vacancies prefer the nearest neighboring sites of Zr4+ as in yttria-stabilized zirconia. The formation enthalpy from binary oxides, fluorite CeO2, monoclinic ZrO2 and C-type YO1.5, (ΔHf,ox) is also slightly positive, varying analogously to ΔHf,ss.