© 2018. Background: The International Committee on Mental Health (ICMH) published screening guidelines in Cystic Fibrosis (CF). This work 1) evaluated the sensitivity of the recommended screening tools against the 'gold standard' clinical psychological assessment and 2) investigated referral and treatment pathways. Methods: Ninety-six participants (79 caregivers; 17 adolescents with CF) completed the screening tools prior to formal assessment. Agreement between screening data and psychological assessment was evaluated, sensitivity analyses performed and referral pathways tracked. Results: All participants with an elevated screen (moderate/severe range) were subsequently assessed as requiring treatment for major depression/anxiety disorders. However, many were referred for treatment without elevated scores. Hence, sensitivity was poor with the recommended threshold score of 10, but with a threshold of 5 the sensitivity was 76% for adults and 46% for adolescents. The area under the ROC curve (diagnostic test ability) was 0.89 for caregivers but lower at 0.68 for adolescents. Conclusion: Mental health screening is complex, particularly in adolescents. Nonetheless, it is a first valuable step to improve mental health care in CF. The need for psychological support is greater than anticipated by the TIDES study.