We applied the AirQ+ model to analyze the 2021 data within our study period (15 December 2020 to 17 June 2022) to quantitatively estimate the number of specific health outcomes from long- and short-term exposure to atmospheric pollutants that could be avoided by adopting the new World Health Organization Air Quality Guidelines (WHO AQGs) in São Paulo, Southeastern Brazil. Based on temporal variations, PM2.5, PM10, NO2, and O3exceeded the 2021 WHO AQGs on up to 54.4% of the days during sampling, mainly in wintertime (June to September 2021). Reducing PM2.5values in São Paulo, as recommended by the WHO, could prevent 113 and 24 deaths from lung cancer (LC) and chronic obstructive pulmonary disease (COPD) annually, respectively. Moreover, it could avoid 258 and 163 hospitalizations caused by respiratory (RD) and cardiovascular diseases (CVD) due to PM2.5exposure. The results for excess deaths by RD and CVD due to O3were 443 and 228, respectively, and 90 RD hospitalizations due to NO2. Therefore, AirQ+ is a useful tool that enables further elaboration and implementation of air pollution control strategies to reduce and prevent hospital admissions, mortality, and economic costs due to exposure to PM2.5, O3, and NO2in São Paulo.