The O-exchange reaction between CO2+ and CO is triggered by two different entrance channels in 13C-labeled systems. The unimolecular dissociation of the C13CO3+ reactive intermediate is investigated at varyingenergies by mass spectrometric techniques. An almost “one-way” O-exchange at energies close to thedissociation threshold discloses a remarkably large intramolecular 12C/13C kinetic isotope effect ranging from6.0 to 7.3 ± 0.5.