The relationship between COVID-19 infections and environmental contaminants provides insight into how environmental factors can influence the spread of infectious diseases. By integrating epidemiological and environmental variables into a mathematical framework, the interaction between virus spread and the environment can be determined. The aim of this study was to evaluate the impact of atmospheric contaminants on the increase in COVID-19 infections in the city of Quito through the application of statistical tests. The data on infections and deaths allowed to identify the periods of greatest contagion and their relationship with the contaminants O3, SO2, CO, PM2.5, and PM10. A validated database was used, and statistical analysis was applied through five models based on simple linear regression. The models showed a significant relationship between SO2 and the increase in infections. In addition, a moderate correlation was shown with PM2.5, O3, and CO, and a low relationship was shown for PM10. These findings highlight the importance of having policies that guarantee air quality as a key factor in maintaining people’s health and preventing the proliferation of viral and infectious diseases.