To successfully meet the demands of the social environment, individuals must adaptively respond to social stressors. Early life stress (ELS) and loneliness are two types of social stressors associated with a variety of adverse psychological and physiological outcomes in adulthood. Empathy also plays an influential role in the social environment by fostering the formation and maintenance of interpersonal relationships. While prior research explores the relationships between ELS and loneliness and/or empathy and loneliness, the interactions between these variables have not been well established. The current study investigates the interactions between social stressors (i.e., ELS, loneliness) and empathy, in addition to their associations with two measures of autonomic nervous system (ANS) reactivity: heart rate (HR) reactivity and high- frequency heart rate variability (HF-HRV) reactivity. Participants (N = 119) completed a series of questionnaires to assess ELS, loneliness, and empathy, and a subset of participants (n = 41) underwent a social stress manipulation to assess physiological reactivity to an acute social stressor. Consistent with prior research, higher levels of ELS predicted higher levels of loneliness. Furthermore, emotional abuse (EA) interacted with cognitive empathy to predict loneliness in adulthood, such that at higher levels of EA, lower levels of cognitive empathy corresponded to increased loneliness. The study also revealed that sexual abuse (SA) and physical abuse (PA) were positively associated with HF-HRV reactivity, and cognitive empathy was positively associated with HR reactivity. Conversely, loneliness showed a significant negative association with HF- HRV reactivity. These findings elucidate the relationships between social stressors, empathy, and physiological stress reactivity, and provide broader insight into how individuals respond to stressors in the social environment.