We investigate the seasonal variability of the southern tip (30°-38°S) of the eastern South Pacific oxygen minimum zone (OMZ) based on a high horizontal resolution (1/12°) regional coupled physical-biogeochemical model simulation. The simulation is validated by available in situ observations and the OMZ seasonal variability is documented. The model OMZ, bounded by the contour of 45 μM, occupies a large volume (4.5x10 4 km 3 ) during the beginning of austral winter and a minimum (3.5x10 4 km 3 ) at the end of spring, just 1 and 2 months after the southward transport of the Peru-Chile Undercurrent (PCUC) is maximum and minimum, respectively. We showed that the PCUC significantly impacts the alongshore advection of dissolved oxygen (DO) modulating the OMZ seasonal variability. However, zonal transport of DO by meridionally alternating zonal jets and mesoscale eddy fluxes play also a major role in the seasonal and spatial variability of the OMZ. Consistently, a DO budget analysis reveals a significant contribution of advection terms to the rate of change of DO and the prominence of mesoscale variability within the seasonal cycle of these terms. Biogeochemical processes and horizontal and vertical mixing, associated with subgrid scale processes, play only a secondary role in the OMZ seasonal cycle. Overall, our study illustrates the interplay of mean and (mesoscale) eddy-induced transports of DO in shaping the OMZ and its seasonal cycle off Central Chile.Plain Language Summary Dissolved oxygen in the ocean strongly impacts most marine ecosystems. Its distribution depends mainly on physical and biogeochemical processes. In the eastern South Pacific, water with very low oxygen is present at intermediate depths (100-800 m). This oxygen minimum zone (OMZ) is associated with a regional water mass called Equatorial Subsurface Water which is transported southward along the coast by the Peru-Chile Undercurrent. Here, using a physical/biogeochemical model we investigate the main mechanisms controlling the seasonal variability of the OMZ off central Chile. We found that the total volume of the low-oxygen waters is reduced by 25% during spring. This seasonal change is closely related to changes in the water mass composition and is mainly driven by changes in the undercurrent transport, but zonal currents and eddy fluxes, largely related to mesoscale variability, play also a major role in the seasonal and spatial variability of the OMZ, while biogeochemical and mixing processes play only a secondary role.