Dissolved oxygen (O₂) is essential for most ocean ecosystems, fuelling organisms’ respiration and facilitating the cycling of carbon and nutrients. Oxygen measurements have been interpreted to indicate that the ocean’s oxygen-deficient zones (ODZs) are expanding under global warming. However, models provide an unclear picture of future ODZ change in both the near term and the long term. Studies of past climates can help explore the possible range of ODZ changes in warmer-than-modern periods. Our geochemical measurementsindicate that water-column denitrification in the eastern tropical North Pacific was systematically reduced during the most important periods of sustained global warming of the past 65 million years. Because denitrification is restricted to oxygen-poor waters, our results indicate that in these periods  ODZs were contracted, not expanded. Thus, our results suggest that that global warming may eventually cause ODZ contraction.