Tropical Instability Vortices (TIVs) have a major influence on the physics and biogeochemistry of the equatorial Pacific. Using an eddy-resolving configuration of the Community Earth System Model (CESM-HR) and Lagrangian particle tracking, we examine TIV impacts on the three-dimensional structure and variability of dissolved oxygen (O2) in the upper equatorial Pacific water column. In CESM-HR, the simulated generation and westward propagation of TIVs from boreal summer through winter lead to the seasonal oxygenation of the upper northern equatorial Pacific, exhibited as a deepening of hypoxic depth west of 120ºW. TIV effects on the equatorial Pacific oxygen balance are dominated by eddy-advection and mixing, while indirect TIV effects on O2 consumption play minor roles. These advective effects reflect the transient displacements of isopycnals by eddy pumping as well as vortex transport of oxygen by eddy trapping, stirring, and subduction. TIVs influence on the upper equatorial Pacific O2 distribution and variability has important implications for understanding and modeling marine ecosystem dynamics and habitats, and should be taken into consideration in designing observation networks in this region.