A significant reduction in hospitalizations for acute exacerbations of COPD (AECOPDs) has been reported during the coronavirus disease 2019 (COVID-19) pandemic. It remains unclear whether this reduction is the result of health care avoidance by patients, or of infection prevention and control (IPC) measures. Our objective was to explore the impact of COVID-19-related IPC measures on the occurrence of AECOPD in a real-life inpatient pulmonary rehabilitation (PR) setting, thereby ruling out potential effects of health care avoidance. Patients with COPD admitted for 8 weeks of inpatient PR at Ciro (Horn, the Netherlands) between October 2020 and March 2021, the first winter with full COVID-19-related IPC measures,were compared to patients admitted during the same period in previous years (2017-2018, 2018-2019, and 2019-2020). Electronic medical records were retrospectively screened for the occurrence of moderate to severe AECOPDs, drop-out, and mortality. A total of 501 patients with COPD (median age 66.6 [interquartile range (IQR) 60.3-71.9] years, 43.1% male, forced expiratory volume in 1 second [FEV1] 35.9 [26.8-50.6] % predicted) were analyzed. During 2020-2021, 22 patients (31.0%) experienced ≥1 AECOPD compared to 43 patients (33.6%) in 2019-2020, 55 patients (36.9%) in 2018-2019, and 83 patients (54.2%) in 2017-2018. This represents a 25.4% reduction in 2020-2021 compared to the average of the previous 3 periods, p=0.077. No differences in AECOPD severity, drop-out, or mortality were observed. COVID-19-related IPC measures did not significantly reduce the AECOPD rate during inpatient PR in a single-center setting. The current findings suggest that avoidance of health care may be an important factor in the observed reduction of AECOPD-related hospitalizations during the pandemic and that the value of the strict COVID-19-related IPC measures for the prevention of AECOPDs warrants further research.