Abstract The initial stages of the hydration process have been simulated on a single-Ca(I) terminated hydroxyapatite (0 0 0 1) surface in step-by-step fashion using periodic slab density functional theory (DFT). Adsorption configurations and energetic properties have been described at different H 2O coverage. At low H 2O coverage, oxygen prefers to form Ca O bonds with surface Ca cations, but as coverage increases, H 2O tends to loosely float on the already-formed water layer. The height of the first layer H 2O relative to the surface is found to be 1.6 Å. The hydration process does not cause the decomposition of surface phosphate groups and hydroxyl channel, but does affect the energetics of subsequent Zn substitution and occupation on Ca(I) and Ca(II) sites. The Ca(II) vacancy site is found to be energetically more favorable for occupation due to less spatial constraint. This suggested mechanism of preferential occupation is different from previous attempts to explain the cation substitution site preference in bulk by ionic radius and electronegativity differences.