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Background: There is increasing evidence demonstrating the importance of the neighbourhood built environment in supporting physical activity. Physical activity provides numerous health benefits including improvements in health-related fitness (i.e., muscular, cardiorespiratory, motor, and morphological fitness). Emerging evidence also suggests that the neighbourhood built environment is associated with health-related fitness. Our aim was to summarize evidence on the associations between the neighbourhood built environment and components of health-related fitness in adults. Methods: We undertook a systematic review following PRISMA guidelines. Our data sources included electronic searches in MEDLINE, Embase, CINAHL, Web of Science, SPORTDiscus, Environment Complete, ProQuest Dissertations and Theses, and Transport Research International Documentation from inception to March 2021. Our eligibility criteria consisted of observational and experimental studies estimating associations between the neighbourhood built environment and health-related fitness among healthy adults (age ≥ 18 years). Eligible studies included objective or self-reported measures of the neighbourhood built environment and included either objective or self-reported measures of health-related fitness. Data extraction included study design, sample characteristics, measured neighbourhood built environment characteristics, and measured components of health-related fitness. We used individual Joanna Briggs Institute study checklists based on identified study designs. Our primary outcome measure was components of health-related fitness (muscular; cardiorespiratory; motor, and morphological fitness). Results: Twenty-seven studies (sample sizes = 28 to 419,562; 2002 to 2020) met the eligibility criteria. Neighbourhood destinations were the most consistent built environment correlate across all components of health-related fitness. The greatest number of significant associations was found between the neighbourhood built environment and morphological fitness while the lowest number of associations was found for motor fitness. The neighbourhood built environment was consistently associated with health-related fitness in studies that adjusted for physical activity. Conclusion: The neighbourhood built environment is associated with health-related fitness in adults and these associations may be independent of physical activity. Longitudinal studies that adjust for physical activity (including resistance training) and sedentary behaviour, and residential self-selection are needed to obtain rigorous causal evidence for the link between the neighbourhood built environment and health-related fitness. Trial registration: Protocol registration: PROSPERO number CRD42020179807. [ABSTRACT FROM AUTHOR]