Abstract: Vacuum ultraviolet (VUV) photoionization and dissociative photoionization of capecitabine and its metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 50-deoxy-5- fluorouridine (5'-DFUR), were investigated with infrared laser desorption/tunable synchrotron VUV pho-toionization mass spectrometry. Molecular ions (M+) with small amounts of fragments can be found for these compounds at relatively low photon energies, while more fragment ions would be produced by increasing the photon energies. (M-H₂O)⁺, (base+H)⁺, (base+2H)⁺,(base+30)⁺, (base+60)⁺, and sugar moiety were proposed for these nucleoside drugs with similar backbones. Decomposition channels for the major fragments were discussed in de-tail. Moreover, ab initio calculations were introduced to study the dehydration pathways of three fluoro-nucleosides. Corresponding appearance energies for the (M-H₂O)⁺ ions were computed.