Cu(II)-grafted SBA-15 functionalized S-methylisothiourea aminated epibromohydrin (SBA-15/E-SMTU-Cu-II) as a novel and efficient, heterogeneous mesoporous catalyst was synthesized and characterized by different techniques, such as FT-IR, BET, small-angle XRD, FE-SEM, TEM, TGA, ICP-OES and CHNS analysis. The as-synthesized catalyst revealed a superior catalytic activity towards the one-pot synthesis of tetrahydropyridine derivatives through the pseudo five-component reactions of aromatic aldehydes, aromatic amines and ethyl/methyl acetoacetate, in ethanol at room temperature. Importantly, the synthesized mesoporous catalyst can be recovered and reused at least ten times without any appreciable loss in its catalytic reactivity. Moreover, a TEM image of the recovered catalyst after ten consecutive runs clearly proved the advantageous durability and stability of the presented catalyst under the applied reaction condition.