The isotopic fractionation associated with the O + CO reaction has been studied using oxygen atoms produced by room temperature O2 photolysis at two different wavelengths, 185 and 130 nm. A large mass-independent isotopic fractionation is observed in the product CO2, extending the range of this type of reaction beyond O + O2 and SF5 + SF5. Kinetic evaluation of the data restricts the source of the mass-independent fractionation mechanism to the O + CO recombination step rather than O2 photolysis, secondary ozone formation, or O2 photodissociation. At least one, and most likely two other fractionation processes appear to occur in the experiments, and interpretation of the isotopic results is tentative at present. Based on the relevant reaction rates and the value for the reduced partition function for isotopic exchange between O and CO, it is suggested that this process may occur prior to the δ17O≅δ18O recombination process. Secondary CO2 photolysis may superimpose an additional fractionation. The experimental data are also examined in the context of a model based upon energy randomization rates versus the lifetime of the activated complex.