Aim: To perform a systematic review establishing the current evidence base for physical activity and exercise interventions that promote health, fitness and wellbeing, rather than specific functional improvements, for children who use wheelchairs. Design: A systematic review using a mixed methods design. Data sources: A wide range of databases including Web of Science, PubMed, BMJ Best Practice, NHS EED, CINAHL, AMED, NICAN, PsychINFO were searched for quantitative, qualitative and health economics evidence. Eligibility: participants: children/young people aged >25 years who use a wheelchair, or parents and therapists/carers. Intervention: home or community-based physical activity to improve health, fitness and wellbeing. Results: Thirty quantitative studies that measured indicators of health, fitness and wellbeing, and one qualitative study were included. Studies were very heterogeneous preventing a meta-analysis, and the risk of bias was generally high. Most studies focused on children with cerebral palsy and utilised an outcome measure of walking or standing, indicating that they were generally designed for children with already good motor function and mobility. Improvements in health, fitness and wellbeing were found across the range of outcome types. There were no reports of negative changes. No economics evidence was found. Conclusions: It was found that children who use wheelchairs can participate in physical activity interventions safely. The paucity of robust studies evaluating interventions to improve health and fitness is concerning. This hinders adequate policy making and guidance for practitioners, and requires urgent attention. However, the evidence that does exist suggests that children who use wheelchairs are able to experience the positive benefits associated with appropriately designed exercise.