Complexes of encapsulated metal ions are promising potential metal-based electron paramagnetic resonance imaging (EPRI) agents due to zero-field splitting. Herein, we synthesize and magnetically characterize a series of five new Ni(II) complexes based on a clathrochelate ligand to provide a new design strategy for zero-field splitting in an encaged environment. UV-Vis and X-ray single-crystal diffraction experiments demonstrate slight physical and electronic structure changes as a function of the differing substituents. The consequence of these changes at the remote apical and sidearm positions of the encaging ligands is a zero-field splitting parameter (D) that varies over a large range of 11 cm⁻¹. These results demonstrate a remarkable flexibility of the zero-field splitting and electronic structure in nickelous cages and give a clear toolkit for modifying zero-field splitting in highly stable ligand shells.