BACKGROUND AND PURPOSE: Pain has been reported in cystic fibrosis (CF), but its clinical significance and the physical and psychosocial impact in adults who are clinically stable and acutely unwell have not been well described. The aim of this study was to describe the intensity and location of pain and its relationship with health-related quality of life (HRQOL) and pain catastrophizing in adults with CF. METHODS: This study was an observational study of adults with CF. Participants completed three questionnaires, the Brief Pain Inventory, Pain Catastrophizing Scale and the CF-Quality of Life questionnaire, when clinically stable and during an acute exacerbation. RESULTS: A total of 73 participants were included during a period of clinical stability, with 33 repeating the measurements during an acute illness, with a mean (SD) age of 29 (9) years and forced expiratory volume (FEV(1) ) of 60.5 (24.9)% predicted. Mild pain was reported by 89% of stable participants and 79% of those with exacerbations. Severity of lung disease did not affect prevalence or intensity of pain. Pain interfered with airway clearance therapy during exacerbations (p < 0.012) and exercise regimens when participants were clinically stable (p < 0.002) and was related to a poorer physical function, regardless of clinical status (p < 0.05). Although pain intensity was associated with reduced HRQOL (p < 0.001), only FEV(1) and the degree of pain catastrophizing were independent predictors of poorer HRQOL. CONCLUSIONS: Pain is common in adults with CF, irrespective of clinical status, and may interfere with important physiotherapy treatments. Although pain intensity is generally mild, those with a negative emotional response to pain have significantly impaired HRQOL.