Depressive symptoms have been associated with lower cardiac autonomic control, thus contributing to cardiovascular diseases, especially among older adults. Interpersonal factors have been found to attenuate physiologic stress responses, but little is known about whether these factors (e.g., perceived affiliation) would moderate the relation of depressive symptoms and cardiovascular activation. The present research aimed to investigate the interplay of depressive symptoms and momentary-assessed interpersonal perceptions on cardiac vagal tone as indexed by heart rate variability (HRV). The sample consisted of 78 late middle-aged and older community-dwelling participants (48.7% male, mean age = 59.15 years). Participants reported on depressive symptoms and other personal characteristics by questionnaire. Perceptions of interpersonal affiliation, ambulatory HRV, and contextual variables were recorded using ecologic momentary assessment and portable electrocardiogram (ECG) monitoring device throughout 1 week (with a maximum of seven times daily). Multilevel analyses found that depressive symptoms were correlated with lower HRV, whereas momentary interpersonal perceptions of higher affiliation were associated with elevated HRV. A significant association was revealed between depressive symptoms and momentary affiliation perceptions on HRV. When individuals were involved in social interactions with higher affiliation, the effect of depressive symptoms on reducing HRV was attenuated. These findings suggested that the effects of subthreshold depressive symptoms on vagal control of the heart could be altered by the quality of interpersonal experiences.