3-Pentadecafluoroheptyl, 5-perfluorophenyl-1,2,4-oxadiazole (FOX) molecules were attached onto a graphene oxide (GO) via a facile aromatic substitution in alkaline environment. This approach allows achieving high degree of functionalization under mild conditions. The covalent attachment of perfluoromoieties onto GO lamellae was confirmed by spectroscopic analyses. The performance of these nanoplatforms (GOF) as oxygen reservoirs was assessed at different concentrations and temperature. The results revealed that under physiologic conditions GO and FOX synergistically operate for increasing oxygen uptake and release, either from a thermodynamic and a kinetic point of view. Even at low concentrations, GOF showed values in terms of oxygen content at saturation and diffusion rate higher than those of other materials currently proposed as O-2-reservoirs in tissue engineering, for cell oxygenation during the regeneration of vascularized tissues. Furthermore, GOF displayed a high cytocompatibility. These findings open new, intriguing scenarios for a further application field of graphene-derived materials.