Rationale: COPD patients often report poor sleep quality. The correlates of sleep quality over time are not well described. We used a large sample of moderate to severely ill COPD patients to: (1) describe sleep quality at baseline and over 1 year, (2) describe patient and treatment factors predicting sleep quality, (3) compare good vs. poor sleepers’ on subscales of health-related (HrQOL) and disease-specific (DsQOL) quality of life, (4) describe the variance in HrQOL and DsQOL explained by sleep quality. Methods: Data were taken from a large (N = 1117) multisite trial of azithromycin therapy in COPD. At baseline, 3 and 12 months, we examined sleep quality (Pittsburgh Sleep Quality Index), DsQOL (St. George’s Respiratory Questionnaire) and HrQOL (SF-36) in association with patient (demographic, comorbidities, disease severity) and treatment factors (medications, oxygen, inhaled drugs). Results: Baseline sleep quality was poor (Pittsburgh score >5) in 53% of participants; yet only 20% reported daytime dysfunction due to poor sleep. The following were associated with better sleep quality (lower PSQI scores): younger age, male gender, white race, higher educational level, not currently smoking, no lifetime periods of daily at-risk alcohol use, higher household income, and lower FEV1. Use of oxygen and specific inhaled medication classes were not associated with different sleep quality. Excluding patients in whom exacerbations occurred prior to the sleep measure, sleep quality was stable over 12 months in half the patients. Good sleepers showed better scores for both HrQOL and DsQOL. Patients with comorbid ischemic heart disease, ulcer disease, anxiety and depression had worse sleep quality. Sleep quality explained 6-8% of the variance in HrQOL and DsQOL. Conclusions: Patients with moderate to severe COPD report a high prevalence of poor sleep quality. Common co-morbidities associated with COPD may influence this relationship. There is an association between sleep quality and both DsQOL and HrQOL. In spite of the high prevalence of poor sleep, relatively few COPD patients reported excessive daytime sleepiness.