The COVID-19 pandemic has imposed a unique situation for humanity, reaching up to 5623 deaths in Sao Paulo city during the analyzed period of this study. Due to the measures for social distancing, an improvement of air quality was observed worldwide. In view of this scenario, we investigated the air quality improvement related to PM10, PM2.5, and NO2 concentrations during 90 days of quarantine compared to an equivalent period in 2019. We found a significant drop in air pollution of 45% of PM10, 46% of PM2.5, and 58% of NO2, and using a relative-risk function, we estimated that this significant air quality improvement avoided, respectively, 78, 337, and 387 premature deaths, respectively, and prevented approximately US $720 million on health costs. Moreover, we estimated that 5623 deaths by COVID-19 represent an economic health loss of US $10.5 billion. Both health and economic gains associated with air pollution reductions give a positive perspective of the efforts towards keeping air pollution reduced even after the pandemic, highlighting the importance of improving the strategies of air pollution mitigation actions, as well as the crucial role of adopting efficient measures to protect human health both during and after the COVID-19 global health crisis.