Metal-organic frameworks (MOFs) with coordinatively unsaturated metal sites are appealing as adsorbent materials due to their tunable functionality and ability to selectively bind small molecules. Through the use of computational screening methods based on periodic density functional theory, we investigate O-2 and N-2 adsorption at the coordinatively unsaturated metal sites of several MOF families. A variety of design handles are identified that can be used to modify the redox activity of the metal centers, including changing the functionalization of the linkers (replacing oxido donors with sulfido donors), anion exchange of bridging ligands (considering mu-Br-, mu-Cl-, mu-F-, or mu-OH- groups), and altering the formal oxidation state of the metal. As a result, we show that it is possible to tune the O-2 affinity at the open metal sites of MOFs for applications involving the strong and/or selective binding of O-2. In contrast with O-2 adsorption, N-2 adsorption at open metal sites is predicted to be relatively weak across the MOF dataset, with the exception of MOFs containing synthetically elusive V2+ open metal sites. As one example from the screening study, we predicted that exchanging the mu-Cl- ligands of M2Cl2(BBTA) (H(2)BBTA = 1H,SH-benzo(1,2-d:4,5-d')bistriazole) with mu-OH- groups would significantly enhance the strength of O-2 adsorption at the open metal sites without a corresponding increase in the N-2 affinity. Experimental investigation of Co2Cl2(BBTA) and Co-2(OH)(2)(BBTA) confirms that the former exhibits weak physisorption of both N-2 and O-2, whereas the latter is capable of chemisorbing O-2 at room temperature in a highly selective manner. The O-2 chemisorption behavior is attributed to the greater electron-donating character of the mu-OH- ligands and the presence of H-bonding interactions between the mu-OH- bridging ligands and the reduced O-2 adsorbate.