ObjectiveMechanisms underlying the relationship between physical activity and quality of life (QOL) in breast cancer survivors are not well understood. The purpose of the present study was to longitudinally test a model examining self-efficacy and health status as potential mediators of this relationship. MethodsAt baseline and 6months, breast cancer survivors (n=1527) completed physical activity, self-efficacy, health status, and QOL measures, and a subsample (n=370) wore an accelerometer. Panel analysis within a covariance modeling framework was used to test the hypothesis that physical activity indirectly influences QOL across time. ResultsThe hypothesized model provided a good fit in the full sample ((2)=409.06; d.f.=91, p<0.001; comparative fit index (CFI)=0.98; standardized root mean residual (SRMR)=0.04) and the accelerometer subsample ((2)=320.96, d.f.=134, p<0.001; CFI=0.95; SRMR=0.05), indicating that physical activity indirectly, via self-efficacy and health status indicators, influences QOL across time. ConclusionsPhysical activity may influence QOL in breast cancer survivors through more proximal, modifiable factors. Copyright (c) 2013 John Wiley & Sons, Ltd.