Thermal dissociation of the cationic niobium vanadium oxide clusters, NbnVmOk+ (n + m = 2-8), was investigated by gas phase thermal desorption spectrometry. The oxygen-rich NbnVmOk+ released O and O-2 for odd and even values of n + m, respectively. Substitution of more than one Nb atom in NbnOk+ by V drastically lowered the desorption temperature of O-2 for even values of n + m, whereas the substitution of more than two Nb atoms opened a new desorption path involving the release of O-2 for odd values of n + m. The substitution effects can be explained by the fact that Nb atoms display the +5 state, whereas V atoms can exist in either the +4 or +5 states. The geometrical structures of selected NbnVmOk+ clusters were optimized and the energetics of the release of O/O-2 from the clusters was discussed on the basis of the results of DFT calculations.