In addition to the detrimental health consequences, the early stages of the COVID-19 pandemic have yielded unforeseen benefits in terms of reducing air pollution emissions. This study investigated air pollution changes in Novi Sad, Serbia, during the COVID-19 lockdown (March–June 2020) and their correlation with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) hospitalizations. Using quasi-Poisson generalized linear models (GLM) and distributed lag non-linear models (DLNM), we examined the relationship between the number of AECOPD hospitalizations and the concentrations of selected air pollutants (PM10, PM2.5, SO2, and NO2) from March to June of 2019, 2020, and 2021. During the COVID-19 lockdown, significant reductions in most air pollutant concentrations and the number of AECOPD hospitalizations were observed. However, neither the study year nor its interaction with air pollutant concentration significantly predicted AECOPD hospitalizations (p > 0.05). The 95% confidence intervals of the relative risks for the occurrence of AECOPD hospitalizations at each increase in the examined air pollutant by 10 μg/m3 overlapped across years, suggesting consistent effects of air pollution on the risk of AECOPD hospitalizations pre-pandemic and during lockdown. In conclusion, reduced air pollution emissions during the COVID-19 lockdown did not lead to a statistically significant change in the number of AECOPD hospitalizations.