Limitations of current depression treatments may arise from a lack of knowledge about unique psychophysiological processes that contribute to depression across the full range of presentations. This study examined how individual variations in heart rate (HR) and heart rate variability (HRV) are related to depressive symptoms across normative and clinical populations in 152 young adults (aged 18-35 years). Moderating effects of sex and antidepressant medication status were considered. Electrocardiogram data were collected during "vanilla" baseline and in response to positive and negative emotional cues. Linear regressions and repeated-measures mixed models were used to assess the relationships between Beck Depression Inventory-II (BDI-II) scores, sex, antidepressant use, and cardiovascular outcomes. Baseline models yielded significant main effects of BDI-II and sex on HR and significant interactions between antidepressant medication status and BDI-II on HRV outcomes. The main effects of BDI-II and sex on HR were no longer significant after controlling for cardiorespiratory fitness. Participants who denied current antidepressant use (n = 137) exhibited a negative association and participants who endorsed current antidepressant (n = 15) use exhibited a positive association between BDI-II scores and HRV. Emotional reactivity models were largely non-significant with the exception of a significant main effect of antidepressant medication status on high-frequency HRV reactivity. Results indicated antidepressant medication use may moderate the relationship between depression severity and cardiovascular functioning, but this requires replication given the modest proportion of medicated individuals in this study. Overall, findings suggest cardiovascular processes and cardiorespiratory fitness are linked to depression symptomatology and may be important to consider in depression treatment.