Hypolimnetic oxygenation systems (HOx) are increasingly used in lakes and reservoirs to elevate dissolved oxygen (O2) while preserving stratification, thereby decreasing concentrations of reduced chemical species in the hypolimnion. By maintaining an oxic zone in the upper sediment, HOx suppress fluxes of reduced soluble species from the sediment into the overlying water. However, diminished HOx performance has been observed due to HOx-induced increases in sediment O2 uptake. Based on a series of in situ O2 microprofile and current velocity measurements, this study evaluates the vertical O2 distribution at the sediment-water interface as a function of HOx operation. These data were used to determine how sediment O2 uptake rate (JO2) and sediment oxic-zone depth (z max) were affected by applied oxygen-gas flow rate, changes in near-sediment mixing and O2 concentration, and proximity to the HOx. The vertical sediment-water O2 distribution was found to be strongly influenced by oxygenation on a reservoir-wide basis. Elevated JO2 and an oxic sediment zone were maintained during continuous HOx operation, with z max increasing linearly with HOx flow rate. In contrast, JO2 decreased to zero and the sediment became anoxic as the vertical O2 distribution at the sediment-water interface collapsed during periods when the HOx was turned off and near-sediment mixing and O2 concentrations decreased. JO2 and z max throughout the reservoir were found to be largely governed by HOx-induced mixing rather than O2 levels in the water column. By quantifying how JO2 and zmax vary in response to HOx operations, this work (1) characterizes how hypolimnetic oxygenation affects sediment O2 dynamics, (2) contributes to the optimization of water quality and management of HOx-equipped lakes and reservoirs, and (3) enhances understanding of the effect of mixing and O2 concentrations in other systems.