The oxidation of CO by N2O over metal-organic framework (MOF) M-3(btc)(2) (M = Fe, Cr, Co, Ni, Cu, and Zn) catalysts that contain coordinatively unsaturated sites has been investigated by means of density functional theory calculations. The reaction proceeds in two steps. First, the N-O bond of N2O is broken to form a metal oxo intermediate. Second, a CO molecule reacts with the oxygen atom of the metal oxo site, forming one C-O bond of CO2. The first step is a rate-determining step for both Cu-3(btc)(2) and Fe-3(btc)(2), where it requires the highest activation energy (67.3 and 19.6 kcal/mol, respectively). The lower value for the iron compound compared to the copper one can be explained by the larger amount of electron density transferred from the catalytic site to the antibonding of N2O molecules. This, in turn, is due to the smaller gap between the highest occupied molecular orbital (HOMO) of the MOF and the lowest unoccupied molecular orbital (LUMO) of N2O for Fe-3(btc)(2) compared to Cu-3(btc)(2). The results indicate the important role of charge transfer for the N-O bond breaking in N2O. We computationally screened other MOF M-3(btc)(2) (M = Cr, Fe, Co, Ni, Cu, and Zn) compounds in this respect and show some relationships between the activation energy and orbital properties like HOMO energies and the spin densities of the metals at the active sites of the MOFs.