A large amount of literature has demonstrated that Perceived Criticism (PC)—that is, how critical a person believes a given relative is of him or her—is associated with negative clinical outcomes in a broad range of psychiatric disorders (e.g., relapse or recurrence of symptoms). A possible mechanism behind the predictive value of PC might be its association with the stress regulation process. This is the first study to investigate differences in the psychophysiological response to a social stress task in young women (mean age = 21.66, SD = 4.33) with high (n = 40) and low (n = 39) PC. The physiological response was investigated by measuring two markers of sympathetic activity mediated by acetylcholine (skin conductance levels; SCL) and adrenaline (pre-ejection period; PEP) levels, respectively, and one marker of the vagally-mediated parasympathetic system (heart rate variability; HRV). Moreover, we investigated the anticipation and perception of social threat, in the form of criticism, during the stressor. No differences in HRV and SCL were observed. However, individuals high in PC mobilized fewer cardiovascular resources to deal with the stressor, reflected in an attenuated beta-adrenergic response (i.e., lower PEP response). Women high in PC also expected and perceived more criticism during the stress task. Together, our results indicate that women high in PC make heightened social threat anticipation and interpretations, and they tend to engage in less active coping when exposed to socially evaluated stressful events. Our findings indicate that PC is associated with underlying stress-related psychobiological vulnerabilities that may contribute to its association with negative clinical outcomes.