Introduction: Physical activity and sleep quality have been consistently associated with quality of life (QOL) in a number of clinical and non-clinical populations. However, mechanisms underlying this relationship are not well understood. The purpose of this study was to longitudinally test a model examining how changes in physical activity and sleep quality, predict physical, mental and social well-being and global QoL across a 6-month exercise trial in a sample of healthy older adults. Methods: Participants (N = 247, mean age 65.4 ± 4.6) wore an accelerometer to assess objective levels of physical activity and completed measures of sleep, physical and mental well-being, social well-being and QOL at baseline and following a 6-month physical activity intervention. Relationships among model constructs were examined over time using panel analysis within a covariance-modeling framework. Results: The hypothesized model provided a good model-data fit (χ2 = 58.77, df = 41, p = .036); CFI = 0.98; SRMR = 0.05; RMSEA = 0.04). At both time-points, physical activity and sleep quality were significantly correlated. Sleep quality indirectly influenced QOL via physical, mental and social well-being (QOL R2 = .47, p ' .001). These relationships were also supported across time at month 6 (QOL R2 = .50, p ' .001). Neither physical activity nor sleep quality directly influenced QOL. Conclusion: Our results support a novel sleep and QOL model that may inform the design of health interventions to promote sleep quality, and thereby influencing QOL by targeting physical activity and modifiable mediators of physical, mental and social health. Our findings may have significant implications for older adults as well as clinical populations that report compromised sleep, impaired health related and global QOL.