Patients with Chronic Obstructive Pulmonary Disease (COPD) have a higher prevalence of coronary ischemia and other factors that put them at risk for COVID-19-related complications. We aimed to explore the impact of COVID-19 in a large population-based sample of patients with COPD in Castilla-La Mancha, Spain. We analyzed clinical data in electronic health records from 1 January to 10 May 2020 by using Natural Language Processing through the SAVANA Manager^® clinical platform. Out of 31,633 COPD patients, 793 had a diagnosis of COVID-19. The proportion of patients with COVID-19 in the COPD population (2.51%; 95% CI 2.33–2.68) was significantly higher than in the general population aged >40 years (1.16%; 95% CI 1.14–1.18); p < 0.001. Compared with COPD-free individuals, COPD patients with COVID-19 showed significantly poorer disease prognosis, as evaluated by hospitalizations (31.1% vs. 39.8%: OR 1.57; 95% CI 1.14–1.18) and mortality (3.4% vs. 9.3%: OR 2.93; 95% CI 2.27–3.79). Patients with COPD and COVID-19 were significantly older (75 vs. 66 years), predominantly male (83% vs. 17%), smoked more frequently, and had more comorbidities than their non-COPD counterparts. Pneumonia was the most common diagnosis among COPD patients hospitalized due to COVID-19 (59%); 19% of patients showed pulmonary infiltrates suggestive of pneumonia and heart failure. Mortality in COPD patients with COVID-19 was associated with older age and prevalence of heart failure (p < 0.05). COPD patients with COVID-19 showed higher rates of hospitalization and mortality, mainly associated with pneumonia. This clinical profile is different from exacerbations caused by other respiratory viruses in the winter season.