The thermodynamics of protonation of trans-[Re(V)O(2)L(2)](+) (L = aliphatic di and polyamines) complexes in aqueous solution was studied by using experimental and theoretical approaches. The complexes containing diamines undergo protonation on the oxo ligands, whereas those containing polydentate amines protonate on uncoordinated amino groups. The protonation reactions were studied experimentally by microcalorimetric techniques, in all cases exothermic with |DeltaH degrees | ranging from 7 to 50 kJ/mol. For complexes containing diamines, the exothermicity was in concordance with the basicities in some cases, while in others no systematic behaviour was found. For complexes with polydentate amines, the enthalpy dominates with a modest influence on the entropy. Theoretically, Density Functional Theory (DFT) methods were employed in the gas phase, and bulk solvent effects were treated by means of the Polarizable Continuum Model. Direct solute-solvent effects were considered adding explicit water molecules. The enthalpy change calculated in the gas phase was in marked disagreement with the experimental results due to the relevancy of solvation/desolvation processes. The explicit inclusion of water molecules led to a good improvement. A discrete-continuum model was also employed, for which DeltaG degrees was overestimated in all cases. Further investigations, both experimental and theoretical are necessary to get a more complete picture of the proton transfer reactions of these complexes. The experimental values herein determined constitute the first step to construct a set of data to which it is possible to benchmark new theoretical approaches to compute the thermodynamics of proton transfer reactions of metal complexes in aqueous solution.