Muscle health has not been thoroughly analyzed in pediatric cystic fibrosis (CF) under elexacaftor/tezacaftor/ivacaftor (ETI) therapy together with exercise interventions in randomized controlled trials (RCTs). The aim of this study will be to determine the effects of a virtual live exercise training intervention on muscle health and cardiorespiratory fitness (CRF) variables in a pediatric population with CF under ETI therapy. The 'FIQMODE' Study (FIQ for CF in Spanish, or fibrosis qu & iacute;stica; MOD for modulator therapy; and E for exercise) is a two-arm RCT to evaluate the feasibility and efficacy of a novel exercise intervention to improve the muscle health and quality of life (QoL) of children and adolescents with CF under ETI pharmacological therapies. The exercise group will follow a 16-week, supervised, strength-oriented virtual live exercise training intervention. The control group will follow the standard World Health Organization recommendations for physical activity. Primary outcomes will be muscle health (lower and upper limb strength, respiratory muscle strength, lower limb functional mobility, anthropometry, and body composition) and CRF. Secondary outcomes will be clinical history, lung function, inflammatory status, lifestyle and QoL, adherence, and the Mediterranean Diet Quality Index. Participants will complete measures at baseline (pre-intervention), 16 weeks post-intervention, and 8 months follow-up after the intervention. FIQMODE will provide an evidence-informed protocol for exercise-based therapy focused on outcomes reported in a robust RCT that can be applied across children and adolescents with CF under ETI therapy. FIQMODE will support the standardization of CF therapies with ETI together with exercise therapies, which will maximize the usability of exercise in medical applications, improve muscle quality, reduce pulmonary exacerbation, boost pharmacological improvement, and ultimately help improve the lifestyle of children and adolescents with CF. Trial registration: The protocol has been approved by the Ethics Committee of the Universidad Polit & eacute;cnica de Madrid (REF. 20231215) and registered on ClinicalTrials.gov (NCT06322446). This research was funded by the Instituto de Salud Carlos III, which is co-funded by the European Regional Development Fund (PI 23/00299). The Instituto de Salud Carlos III supported this study through the project agreement "FIQMODE" with the Universidad Polit & eacute;cnica de Madrid (C2311600157). (c) 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.