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Objective Our objectives were to describe trajectories of depressive symptoms and pain at hospital discharge and six weeks later and to examine the relationship of persistent depressive symptoms to pain. Methods Before and six weeks after hospital discharge, 251 cardiac surgery patients (aged 67.3 ± 9.5 years; 73% male) completed the Beck Depression Inventory (BDI) and the Brief Pain Inventory (BPI). Patients were categorized into two groups based on the presence or absence of persistent depressive symptoms (BDI>10 at both times). Between-group differences in pain interference (BPI-INT) and pain severity (BPI-SEV) were evaluated using repeated measures analysis of variance. Linear regressions were performed to determine if changes in depressive symptoms were related to BPI-INT and BPI-SEV, controlling for demographic and clinical data. Results Persistent (16.3%) or worsening depressive symptoms (15.3%) from hospital discharge to six weeks were observed; many experienced at least some persistent pain (BPI-INT - 67.8%; BPI-SEV - 47.8%). From discharge to six weeks, patients with persistent depressive symptoms sustained higher levels of BPI-INT (p<.001) and BPI-SEV (P<.003). In multivariate analysis, only changes in depressive symptoms, not clinical and demographic variables, were related to BPI-INT (p<.001) and BPI-SEV (p=.001). Conclusion Persistent depressive symptoms are independently associated with continued pain up to six weeks after hospital discharge. Successful treatment of ongoing pain should include screening for depressive symptoms and initiation of appropriate treatment.