AbstractSupported atomic metal sites have discrete molecular orbitals. Precise control over the energies of these sites is key to achieving novel reaction pathways with superior selectivity. Here, we achieve selective oxygen (O₂) activation by utilising a framework of cerium (Ce) cations to reduce the energy of 3d orbitals of isolated copper (Cu) sites. Operando X-ray absorption spectroscopy, electron paramagnetic resonance and density-functional theory simulations are used to demonstrate that a [Cu(I)O₂]³⁻ site selectively adsorbs molecular O₂, forming a rarely reported electrophilic η²-O₂ species at 298 K. Assisted by neighbouring Ce(III) cations, η²-O₂ is finally reduced to two O²⁻, that create two Cu–O–Ce oxo-bridges at 453 K. The isolated Cu(I)/(II) sites are ten times more active in CO oxidation than CuO clusters, showing a turnover frequency of 0.028 ± 0.003 s⁻¹ at 373 K and 0.01 bar P_CO. The unique electronic structure of [Cu(I)O₂]³⁻ site suggests its potential in selective oxidation.