Background: While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients. Methods: Twenty-eight CF patients (18M/10F), with a median age of 27 (22-34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39-93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-min walking test, pulmonary function tests and polysomnographic variables, were also analyzed. Results: Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: median anxiety score of 9 (8-11) vs 4 (3-6) (p < 0.0001), median depression score of 7 (5-10) vs 1 (1-4) (p < 0.001), with a positive correlation between ISI and HAD anxiety/depression scores (r = 0.702/r = 0.701, respectively, p < 0.0001). Insomnia was also associated with mMRC dyspnea scale ≥ 2, restless legs syndrome, pain and lower SpO 2 during sleep. Conclusions: The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia. Trial registration: On clinicaltrials.gov (NCT02924818, date of registration: October 5, 2016).