The synthesis and magnetic characterization of vanillin-based Cu(II) mononuclear complexes of formula [Cu(van)2(H2O)(2)](H2O) (van = vanillinate; x = 0, compound 1; x = 2, compounds 2 and 3) were performed. Despite the presence of very similar [Cu(van)(2)(H2O)(2)] moieties, the crystal structures exhibit distinct Cu center dot center dot center dot Cu contacts and display three different through-H-bond exchange-coupling pathways. As a result of the relative positions of the water molecules, the experimental (MAGSUS) exchange-coupling constants are dissimilar, i.e., J(1) = -3.0 cm(-1) (the data have been fitted to the Bleaney-Bowers equation considering a dimer; 2J = -6.0 cm(-1)), J(2) = -4.0 cm(-1) (the data have been fitted to the Bonner-Fischer equation for a chain of monomeric copper(II) units), whereas compound 3 is paramagnetic. Subsequently, the theoretical density functional theory (DFT) and wave function theory-based (DDCI) calculations were carried out to better understand the role of the water molecule as a mediator of the magnetic coupling. The use of localized orbitals allows one to elucidate the role of the H-bonds in generating exchange interactions. Since the exchange-coupling constants are strongly dependent on the mechanisms selectively introduced, the role of the H-bond is demonstrated.