Introduction: The aim of the study was to examine the direct and indirect costs of COPD exacerbations under usual clinical practice in primary and secondary care from a societal perspective in Poland. Material and methods: An observational, prospective study was conducted among patients with exacerbation of moderate or severe COPD. Seventy-three patients were included in the study—39 treated in hospital (HC) and 34 treated in ambulatory care (AC). The direct costs included the cost of drugs, diagnostic tests, in-hospital and outpatient care. The indirect costs included costs of transportation to the health-care provider and work days lost. Results: The mean duration of COPD exacerbation did not differ significantly between the groups [HC: 11.2 (CI 95%: 9.6–12.8) days; AC: 10.8 (CI 95%: 9.1–12.1); p > 0.05]. The total health-care cost per exacerbation was EUR 1197 (4137.9 PLN) in secondary care (the HC group), and it was 6 times higher than the total cost of exacerbation in primary care (the AC group)— EUR 199.8 (446.9 PLN). The costs of drugs and diagnostic tests were significantly higher in the HC group than in the AC group; however, it was the cost of in-hospital stay and medical visits in the HC group that most influenced expenditure related to COPD exacerbations, as they were 27 times higher than in the AC group. Conclusions: In Poland the costs of COPD exacerbation managed in secondary care are 6-fold higher than in primary care. Therefore, the decisions about admission of patients with COPD exacerbation to hospital should be made carefully.