Background : Evidence supporting the individual associations of sedentary behaviours with depression symptoms commonly ignores the inherent co-dependency between physical activity, sedentary behaviours and sleep in a given 24-hour period. Data analysis based on compositional methods effectively deals with this issue. Aim : To investigate the association between sedentary behaviour and depression symptoms synergistically using compositional analysis methods. Methods : Participants were a representative sample of 3,233 US adults and older adults from the 2005-2006 cycle of the NHANES with valid 24-hour lifestyle behaviours data (i.e., accelerometer-derived physical activity and sedentary behaviour and self-reported sleep) and available self-reported depression symptoms (PHQ-9). The association between sedentary behaviour and depression symptoms scoring was investigated using a compositional zero-inflated Poisson regression analysis. Subsequently, the model estimates were used to evaluate the effects on depression symptoms of replacing time spent in sitting activities with physical activity of different intensities and sleep. Limitations : The current study is limited by its cross-sectional design. Also, sleep time was self-reported, which could bias our estimations. Results : Increased sedentary behaviour relative to other behaviours was statistically significantly associated with increased depression symptoms (p < 0.001). Reallocating 60 minutes time from sedentary behaviours to moderate-to-vigorous physical activity (MVPA) and sleep was associated with small reductions in depression symptoms. Conclusions : A synergistic compositional analysis of accelerometer data uncovered a detrimental association between sedentary behaviour and depression symptoms. These results add to evidence from previous studies. The observed association seems to be principally driven by corresponding reductions in MVPA and sleep duration.