introductionYoga is an emerging exercise choice for people with cystic fibrosis (CF), but evidence of its effect in this population is scarce, with a recent systematic review advocating for further research. METHODS AND ANALYSIS: A multicentre RCT of adults with CF across the UK. Participants are randomised to usual care or a 12-week online bespoke yoga programme with an expectation of two classes completed weekly. Assessments of lung function, 1 min sit-to-stand, the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and other trial questionnaires are completed preintervention and postintervention (0 and 12 weeks) and after 12 weeks of follow-up (week 24). The primary outcome is the difference in respiratory-related quality of life measured using the CFQ-R before and after yoga/control. Sample size was calculated based on detecting a minimally clinically important difference of 4 for the CFQ-R respiratory domain, with power of 80% and 5% significance level (total target, n=314). ETHICS AND DISSEMINATION: Ethics approval gained from the South Yorkshire and Humber Research Ethics Committee (REC) (reference: 23/YH/0270, project ID 303898). Dissemination to involve direct participant feedback and lay webinar, scientific conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06120465.