An extensive study has been carried out to evaluate possible use of the perfluoropolyether fluids, obtained from hexafluoropropylene photo-oxidation and specially purified and selected, as lubricants or vacuum-working fluids, in the presence of UF6. Some physicochemical properties are reported and the results of the tests experienced on perfluoropolyether cuts put into contact with UF6 at different conditions for a long aging time at high temperature in the presence of some typical engineering materials. The results allowed a verification of the long-term compatibility of the perfluoropolyether special fractions against UF6 at temperatures up to 130°C.