Background: Chronic medical conditions (CMCs) affect up to 35% of children and adolescents. Youth with chronic medical conditions are at an increased risk of psychological distress and reduced health-related quality of life, and report rates of mental illness up to double that of their physically healthy peers. Accessible, evidence-based interventions for young people with chronic illness are urgently required to improve their mental health and daily functioning. Self-compassion involves taking a mindful, accepting approach to difficult experiences, being aware that one is not alone in one's suffering, and being kind and understanding with oneself during challenging times. Self-compassion shares strong associations with mental health outcomes among young people and preliminary work indicates that interventions that build self-compassion have the potential to substantially improve youth mental health. Self-compassion is also associated with better physical and mental health outcomes among individuals living with CMCs. While face-to-face self-compassion training is available, there are several barriers to access for youth with CMCs. Online self-compassion training potentially offers an accessible alternative for this high-risk group. Methods: Self-Compassion Online (SCO) is a self-compassion program that has been tested with a non-clinical adult group. For the proposed trial, a reference group of youth (16-25 years) with chronic illness reviewed the program and proposed adaptations to improve its suitability for youth with chronic illness. In alignment with the SPIRIT Checklist, this paper outlines the protocol for a CONSORT-compliant, single-blind randomised controlled trial to test the efficacy of the adapted program, relative to a waitlist control, for improving self-compassion, wellbeing, distress, emotion regulation, coping and quality of life among young Australians with CMCs. Mechanisms of action and feasibility of SCO will be analysed using quantitative data and participant interviews, respectively. Finally, cost-utility will be analysed using health-related quality of life data. Discussion: The SCO program could provide a scalable solution for improving psychological outcomes and quality of life among youth with chronic illness. The proposed trial will be the first to determine its efficacy for improving these outcomes, relative to waitlist control.