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Responses to the COVID-19 outbreak resulted in one of the largest short-term decreases in anthropogenic emissions in modern history. To date, there has been no comprehensive assessment of the impact of lockdowns on air quality and human health. Using global satellite observations and ground measurements from 36 countries in Europe, North America, and East Asia, we find that lockdowns led to reductions in NO 2 concentrations globally, resulting in ~32,000 avoided premature mortalities, including ~21,000 in China. However, we do not find corresponding reductions in PM 2.5 and ozone globally. Using satellite measurements, we show that the disconnect between NO 2 and ozone changes stems from local chemical regimes. The COVID-related lockdowns demonstrate the need for targeted air quality policies to reduce the global burden of air pollution, especially related to secondary pollutants., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)