Microcalorimetry was used to study the adsorption of water molecules on the surface of ZnAl2O4 nanoparticles ranging from the anhydrous to the fully hydrated states. Water adsorption of ZnAl2O4 showed similar behavior to the isostructural γ-Al2O3 and revealed possible existence of hydrophobic sites on the surfaces. At the lowest measured coverage (0.49 H2O per nm2), the enthalpy of adsorption is −155.46 kJ/mol. This value decays with increasing coverage and at around 13 H2O per nm2, the heat of adsorption levels at −44 kJ/mol, suggesting further adsorbed water has liquid-like features. The anhydrous surface energy for ZnAl2O4 was calculated to be 1.36 ± 0.08 J/m2 using water adsorption microcalorimetry data. High-temperature oxide melt solution calorimetry was also used to assess the surface energy, which was 1.29 ± 0.33 J/m2. Surface energies at different hydration states are reported and showed decrease with increasing coverage, suggesting that low humidity conditions allow higher driving forces for coarsening.