The Eastern Tropical Pacific (ETP) hosts two of the world’s three Oxygen Deficient Zones (ODZs), large bodies of suboxic water that are subject to high rates of water column denitrification (WCD). In the mean, these two ODZs are responsible for 15 to 40% of all fixed N loss in the ocean, but knowledge is limited on how this loss varies in time. Here, we use hindcast simulations with both a global and a regional model to assess the variability and the extremes in the (de)oxygenation of the ETP and its impact on WCD. Using the global model, i.e., the ocean component of the NCAR Community Earth System Model, we showed already that the El Niño–Southern Oscillation (ENSO) is a major driver for extreme conditions in the ODZ. Namely, we found that ENSO causes large variations in WCD, with mature La Niña (El Niño) conditions having peak denitrification rates that are up to 70% higher (lower) than the mean rates (Yang et al., 2017). This large variability is the result of wind-driven changes in circulation and isopycnal structure concurrently modifying the thermocline distribution of O2and organic matter export in such a way that the response of WCD is strongly amplified. Of particular importance is the shoaling (deepening) of the upper boundary of the ODZs, as this results in a much larger fraction of the exported organic matter being subject to anaerobic remineralization, i.e., WCD. While the global model is well positioned to diagnose and analyze such large-scale events. its usefulness is limited to assess the role of smaller, shorter, but often more intense extreme events. To this end, we will be using hindcast simulations with a high-resolution regional model of the ETP region based on the Regional Oceanic Modeling System (ROMS). Initial analyses suggested that a some of these events are associated with mesoscale eddies that create very strong low oxygen environments, while other events are the result of regional-scale oceanic or atmospheric "weather" conditions. Of particular relevance are those events when ENSO and local processes push the system toward very extreme conditions. Given the highly non-linear nature of the marine oxygen and nitrogen cycle, such extreme events can leave a disproportional impact on the overall (de)oxygenation of the ETP and its WCD, with strong implications on the global-scale balance of the marine N cycle and the emission of the greenhouse gas N2O.