Here we reported the deuteration of the metalbinding equatorial water molecules in a reported Ho III singlemolecule magnet (SMM) with pentagonal-bipyramidal geometry, from [Ho(CyPh 2 PO) 2 (H 2 O) 5 ] 3+ to [Ho(CyPh 2 PO) 2 -(D 2 O) 5 ] 3+ . The hyperfine structures originating from the nuclear spin of 165 Ho III can be clearly observed. Moreover, the resulting magnetization dynamics revealed the switch of the relative relaxation rates for the two isotope-isomorphic complexes-respectively faster/slower at low/high temperature. The noticeable isotope effect arises from not only the paramagnetic metal center but also the diamagnetic ligands, which can be explained by the ab initio calculated tunnel splitting and the involvement of the super-hyperfine interaction related to the difference in the nuclear spin number of protium ( 1 H, I = 1 / 2 ) and deuterium ( 2 H, I = 1).