Background: While chronic morbidity and mortality from COPD is well documented, little is known about the treatment burden faced by patients with COPD. Subjects and methods: Patients with severe airflow obstruction (forced expiratory volume in 1 second [FEV1] <50% predicted) representing different age-groups, sex, and number of comorbidities participated in a semistructured interview. Interviews were conducted until thematic saturation was reached. Interviews were recorded, transcribed, and analyzed thematically using an established treatment-burden framework. Results: A total of 26 patients (42% male, mean age 66.7±9.8 years) with severe (n=15) or very severe (n=11) airflow limitation (mean FEV1 32.1%±9.65% predicted) were interviewed. Participants struggled with various treatment-burden domains, predominantly with changing health behaviors, such as smoking cessation and exercise. Interviewees often only ceased smoking after a major health event, despite being advised to do so earlier by a doctor. Recommended exercise regimens, such as pulmonary rehabilitation classes, were curtailed, although some patients replaced them with light home-based exercise. Interviewees had difficulty attending medical appointments, often relying on others to transport them. Overall, COPD patients indicated they were not willing to accept the burden of treatments where they perceived minimal benefit. Conclusion: This study describes the substantial treatment burden experienced by patients with COPD. Medical advice may be rejected by patients if the benefit of following the advice is perceived as insufficient. Health professionals need to recognize treatment burden as a source of nonadherence, and should tailor treatment discussions to fit patients’ values and capacity to achieve optimal patient outcomes.