Over the past decade, there have been many attempts to engineer systems capable of delivering oxygen to overcome the effects of both systemic and local hypoxia that occurs as a result of traumatic injury, cell transplantation, or tumor growth, among many others. Despite progress in this field, which has led to a new class of oxygen-generating biomaterials, most reported techniques lack the tunability necessary for independent control over the oxygen flux (volume per unit time) and the duration of delivery, both of which are key parameters for overcoming tissue hypoxia of varying etiologies. Here, we show that these critical parameters can be effectively manipulated using hyperbarically-loaded polymeric microcapsules (PMC). PMCs are micron-sized particles with hollow cores and polymeric shells. We show that oxygen delivery through PMCs is dependent on its permeability through the polymeric shell, the shell thickness, and the pressure gradient across the shell. We also demonstrate that incorporating an intermediate oil layer between the polymeric shell and the gas core prevents rapid outgassing by effectively lowering the resultant pressure gradient across the polymeric membrane following depressurization. Display omitted •Oxygen delivery from hyperbarically-loaded polymer microcapsules is feasible.•Oxygen loading and release kinetics from hyperbaric PMCs are highly tunable•PMCs incorporating an intermediate oil layer can be loaded at significantly higher pressures and exhibit greater control over oxygen release compared to their gas-filled counterparts.