Objective: The objective of this study was to examine the cross-sectional and longitudinal relationships between moderate-to-vigorous intensity physical activity (MVPA) and depressive symptoms in women after treatment for breast cancer. Method: Accelerometer data on MVPA and self-report data on frequency of depressive symptoms were collected five times at ∼ 3-month intervals from women (Mage at Time 1 = 55.01 ± 10.96 years) who had completed treatment for breast cancer 3 months prior to study inception. Data were analyzed using latent growth modeling with structured residuals. Results: Levels of MVPA decreased, on average, by .52 min every 3 months (p < .001), whereas the frequency of depressive symptoms was stable. MVPA was inversely and significantly related cross-sectionally with depressive symptoms, but not longitudinally. Also, there was no evidence of a bidirectional predictive relationship between MVPA and depressive symptoms. Conclusion: Although higher levels of MVPA were associated with less frequent depressive symptoms cross-sectionally in women after treatment for breast cancer, MVPA did not predict frequency of depressive symptoms or vice versa. Common etiologic or shared risk factors underpinning the cross-sectional relationships between depressive symptoms and MVPA should be studied across the transition from treatment to survivorship.