A comparative study on the ortho-, meta-, and para-substituted pyridyl groups on the functional motifs of zirconium-based metal-organic frameworks (MOFs) for removing cobalt ions from aqueous solutions was performed. The maximum adsorption capacity of cobalt ions on the ortho-substituted MOF was estimated to be 100.0 mg g(-1) at pH 8.0, which was much higher than those of meta- and para-substituted MOFs. The thermodynamic and kinetic experiments showed that the adsorption was a spontaneous, endothermic, and pseudo-second-order process. The modified MOFs were also demonstrated to have the outstanding regenerated ability by the reusability study. The adsorption mechanism probed by density functional theory calculations indicated that the ortho-substituted pyridine Schiff base can take cobalt ions from both [Co(H2O)(6)](2+) and [Co(CHES)center dot(H2O)(4)](+) to form the bidentate complex [CoLP2 center dot(H2O)(4)](2+), whereas only monodentate complexes could be formed for the other two modified MOFs by substituting one water molecule of [Co center dot(H2O)(6)](2+), which were further confirmed by X-ray photoelectron spectroscopy. This work compares the removal performance of Co(II) from aqueous solutions by the ortho-, meta-, and para-substituted pyridine Schiff bases and provides a guiding route to design and synthesize effective functionalized MOFs for the removal of heavy metals and radionuclides.