Abstract Background COPD is currently the fourth cause of morbidity and mortality in the developed world. Patients with COPD experience a progressive deterioration and disability, which lead to a worsening in their health-related quality of life (HRQoL). The aim of this work is to assess the Health-Related Quality of Life (HRQoL) of patients with stable COPD followed in primary care and to identify possible predictors of disease. Methods It is a multicenter, epidemiological, observational, descriptive study. Subjects of both sexes, older than 40 years and diagnosed of COPD at least 12 months before starting the study were included. Sociodemographic data, severity of disease, comorbidity, and use of health resources in the previous 12 months were collected. All patients were administered a generic quality-of-life questionnaire, the SF-12, that enables to calculate two scores, the physical (PCS-12) and the mental (MCS-12) component summary scores. Results 10,711 patients were evaluated (75.6% men, 24.4% women), with a mean age of 67.1 years (SD 9.66). The mean value of FEV₁ was 35.9 ± 10.0%. Mean PCS-12 and MCS-12 scores were 36.0 ± 9.9 and 48.3 ± 10.9, respectively. Compared to the reference population, patients with COPD had a reduction of PCS-12, even in mild stages of the disease. The correlation with FEV₁ was higher for PCS-12 (r = 0.38) than for MCS-12 (r = 0.12). Predictors for both HRQoL components were sex, FEV₁, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions. Other independent predictors of PCS-12 were age, body mass index and educational level. Conclusion Patients with stable COPD show a reduction of their HRQoL, even in mild stages of the disease. The factors determining the HRQoL include sex, FEV₁, use of oxygen therapy, and number of visits to emergency rooms and hospital admissions.