Redox reactions involving uranium (U) are key processes governing its environmental mobility, accumulation in ore bodies, isotopic fractionation, remediation, and its leaching, extraction, and recovery from mines. Notably, the influx of oxidants, such as dissolved molecular oxygen (DO) or nitrate (NO3−), into aquifers and storage systems threatens long-term sequestration of tetravalent uranium (U4+) minerals via particulate or solid surface dissolution as mobile hexavalent uranium (U6+) species, which can present a significant health risk to those reliant on groundwater. Although nitrate influx is often attributed to anthropogenic inputs, DO naturally infiltrates reduced sediments through advective oxic groundwater flow, rainwater infiltration, and capillary fringe transport. Aquifers also exhibit substantial variations in DO laterally, vertically, and temporally due to variations in soil and rock systems, remediation treatments, and seasonal watershed dynamics. Thus, transitions between oxic and anoxic conditions can result in substantial geochemical changes and stimulation or repression of microbial activity. These reactions with DO are significantly altered by the presence of biomass, metal cations and minerals, (bi)carbonate, and other inorganic ligands. In this chapter, the interactions of DO with uranium species are reviewed and discussed. The influence of DO in practical applications, i.e., uranium extraction and bioremediation, is also examined.