A new oxide cluster fullerene, Sc2O@C-2v(5)-C-80, has been isolated and characterized by mass spectrometry, UV-vis-NIR absorption spectroscopy, cyclic voltammetry, Sc-45 NMR, DFT calculations, and single crystal X-ray diffraction. The crystallographic analysis unambiguously elucidated that the cage symmetry was assigned to C-2v(5)-C-80 and suggests that the Sc2O cluster is ordered inside the cage. The crystallographic data further reveals that the Scl-O-Sc2 angle is much larger than that found in Sc2O@T-d(19151)-C-76 but almost comparable to that in Sc2O@C-s(6)-C-82, suggesting that the endohedral Sc2O unit is flexible and can display large variation in the Sc-O-Sc angle, which depends on the size and shape of the cage. Computational studies show that there is a formal transfer of four electrons from the Sc2O unit to the C-80 cage, i.e., (Sc2O)(4+)@(C-80)(4-), and the HOMO and LUMO are mainly localized on the C-80 framework. Moreover, thermal and entropic effects are seen to be relevant in the isomer selection. Comparative studies between the recently reported Sc2C2@C-2v(5)-C-80 and Sc2O@C-2v(5)-C-80 rev(e)al that, despite their close structural resemblance, subtle differences exist on the crystal structures, and the clusters exert notable impact on their spectroscopic properties as well as interactions between the clusters and corresponding cages.