Introduction: In-bed cycling with patients with critical illness has been shown to be safe and feasible, and improves physical function outcomes at hospital discharge. The effects of early in-bed cycling on reducing the rate of skeletal muscle atrophy, and associations with physical and cognitive function are unknown.

Methods and analysis: A single-centre randomised controlled trial in a mixed medical-surgical intensive care unit (ICU) will be conducted. Adult patients (n=68) who are expected to be mechanically ventilated for more than 48 hours and remain in ICU for a further 48 hours from recruitment will be randomly allocated into either (1) a usual care group or (2) a group that receives usual care and additional in-bed cycling sessions. The primary outcome is change in rectus femoris cross-sectional area at day 10 in comparison to baseline measured by blinded assessors. Secondary outcome measures include muscle strength, incidence of ICU-acquired weakness, handgrip strength, time to achieve functional milestones (sitting out of bed, walking), Functional Status Score in ICU, ICU Mobility Scale, 6 min walk test 1 week post-ICU discharge, incidence of delirium and quality of life (EuroQol Five Dimensions questionnaire Five Levels scale). Quality of life assessments will be conducted post-ICU admission at day 10, 3 and 6 months after acute hospital discharge. Participants in the intervention group will complete an acceptability of intervention questionnaire.

Ethics and dissemination: Appropriate ethical approval from Metro South Health Human Research Ethics Committee has been attained. Results will be published in peer-reviewed publications and presented at scientific conferences to assist planning of future multicentre randomised controlled trials (if indicated) that will test in-bed cycling as an intervention to improve the physical, cognitive and health-related quality of life outcomes of patients with critical illness.