Background: eHealth CF-CBT is the first digital mental health intervention for depression/anxiety in adults with cystic fibrosis (awCF); an 8-session therapist-guided internet-delivered program that was developed in English and Dutch with stakeholder input and evaluation indicating high acceptability and usability. Methods: Dutch eHealth CF-CBT was piloted in awCF with mild-moderate symptoms of depression and/or anxiety. Feasibility, usability, acceptability, and preliminary efficacy were assessed, measuring pre-post changes in depression (PHQ-9), anxiety (GAD-7), perceived stress (PSS) and health-related quality of life (CFQ-R). Results: All participants (n=10, 7 female, mean age 29 (range 21-43), mean FEV1 71%pred (range 31-115)) completed all sessions. Patient-rated feasibility, usability and acceptability of eHealth CF-CBT was positive on validated scales, as were qualitative assessments of content and format. GAD-7 improved in 90% of participants; in 50% by ≥ the minimally important difference (MID) of 4 points. PHQ-9 improved in 90%; 40% by ≥ the MID of 5. PSS improved in 80%. CFQ-R improved in the domain Health Perceptions (70%). Conclusions: eHealth CF-CBT demonstrated feasibility, usability, acceptability and promising preliminary efficacy in this pilot trial with Dutch awCF with mild to moderate symptoms of depression and anxiety.