We have developed an integrated approach that combines synthesis, X-ray photoelectron spectroscopy (XPS) studies, and theoretical calculations for the investigation of active unsaturated metal sites (UMS) in copper-based metal–organic frameworks (MOFs). Specifically, extensive reduction of Cu+2 to Cu+1 at the MOF metal nodes was achieved. Introduction of mixed valence copper sites resulted in significant changes in the valence band structure and an increased density of states near the Fermi edge, thereby altering the electronic properties of the copper-based framework. The development of mixed-valence MOFs also allowed tuning of selective adsorbate binding as a function of the UMS oxidation state. The presented studies could significantly impact the use of MOFs for heterogeneous catalysis and gas purification as well as foreshadow a new avenue for controlling the conductivity of typically insulating MOF materials.