This mixed-method systematic review aims to establish the current evidence base for 'keep fit', exercise or physical activity interventions for children and young people who use wheelchairs. BACKGROUND: Nurses have a vital health promotion, motivational and monitoring role in optimizing the health and well-being of disabled children. Children with mobility impairments are prone to have low participation levels in physical activity, which reduces fitness and well-being. Effective physical activity interventions that are fun and engaging for children are required to promote habitual participation as part of a healthy lifestyle. Previous intervention programmes have been trialled, but little is known about the most effective types of exercise to improve the fitness of young wheelchair users. DESIGN: Mixed-method design using Cochrane systematic processes. Evidence regarding physiological and psychological effectiveness, health economics, user perspectives and service evaluations will be included and analysed under distinct streams. METHODS: The project was funded from October 2012. Multiple databases will be searched using search strings combining relevant medical subheadings and intervention-specific terms. Articles will also be identified from ancestral references and by approaching authors to identify unpublished work. Only studies or reports evaluating the effectiveness, participation experiences or cost of a physical activity programme will be included. Separate analyses will be performed for each data stream, including a meta-analysis if sufficient homogeneity exists and thematic analyses. Findings across streams will be synthesized in an overarching narrative summary. DISCUSSION: Evidence from the first systematic review of this type will inform development of effective child-centred physical activity interventions and their evaluation