Poland has one of the worst air qualities in the European Union, particularly regarding concentrations of particulate matter (PM). This study aimed to evaluate the short-term effects of air pollution and weather conditions on all-cause mortality and pneumonia-related hospitalizations in three Polish agglomerations. We investigated data from 2011 to 2018 on a number of health outcomes, concentrations of PM2.5, PM10, nitrogen dioxide (NO2), ozone (O-3), and selected meteorological parameters. To examine the impact of air pollutants and weather conditions on mortality and pneumonia burden, we identified optimal general regression models for each agglomeration. The final models explained <24% of the variability in all-cause mortality. In the models with interactions, O-3 concentration in Warsaw, NO2, O-3, and PM2.5 concentrations in Cracow and PM10 and O-3 concentrations in the Tricity explained >10% of the variability in the number of deaths. Up to 46% of daily variability in the number of pneumonia-related hospitalizations was explained by the combination of both factors, i.e., air quality and meteorological parameters. The impact of NO2 levels on pneumonia burden was pronounced in all agglomerations. We showed that the air pollution profile and its interactions with weather conditions exert a short-term effect on all-cause mortality and pneumonia-related hospitalizations. Our findings may be relevant for prioritizing strategies to improve air quality.