This study uses the World Health Organization's AirQ + model to assess the relationship between air pollution and mortality in Portugal from 2010 to 2021, focusing on the impact of the COVID-19 pandemic. By integrating AirQ + with Linear Mixed Models, we analyzed long-term air pollution data and its health effects. Results indicate a significant decrease in \(\:{\text{N}\text{O}}_{2}\) and \(\:{\text{P}\text{M}}_{2.5}\) concentrations from 2017–2019 to 2020–2021 due to COVID-19 restrictions and reduced transportation emissions. Conversely, \(\:{\text{O}}_{3}\) exposure slightly increased. The model estimates over 5,000 annual deaths from \(\:{\text{N}\text{O}}_{2}\) and \(\:{\text{P}\text{M}}_{2.5}\) exposure and over 139 annual deaths from \(\:{\text{O}}_{3}\)-related respiratory diseases for 2010–2021. Despite limitations like the need for better assessment of pollutant mixtures and climatic variables, the study shows a decrease in \(\:{\text{N}\text{O}}_{2}\)-related disease burden during the pandemic. These trends reflect anomalies in mortality and pollution data rather than policy improvements. The study underscores the utility of AirQ + in guiding public health strategies and tracking progress towards the 2030 Agenda, offering insights into reducing mortality and morbidity through decreased air pollutant exposure and highlighting the need for sustained, multi-dimensional pollution reduction efforts.