While ostracism constitutes a social stressor with negative effects on physical and mental health, social inclusion seems to increase resilience. This may be true not only for face-to-face settings, but also for computer-mediated interactions. Hence, this study examined the differences between ostracism and social inclusion in real-life or Virtual Reality (VR) regarding self-reported stress, neuroendocrine and cardiovascular reactivity in a subsequent real-life socio-evaluative task. 84 females were randomly assigned to a 3 (agency: face-to-face/human controlled VR-avatar/computer VR-agent) x 2 (inclusion status: inclusion/exclusion) between-subject design using a Cyberball paradigm. Subsequently, they were exposed to a real-life Trier Social Stress Test (TSST). Results indicate that the experience of ostracism constitutes a threat to fundamental social needs independent of agency. Excluded participants showed cardiovascular reactivity during TSST; also face-to-face and avatar excluded individuals had elevated salivary cortisol levels. Included participants reported more perceived social support during Cyberball and showed a blunted cortisol response to the TSST. These results suggest that face-to-face and avatar-related ostracism provokes responses in the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS). Furthermore, they reveal that social inclusion may act as a stress-protector as it alters HPA- and SNS-related stress responsiveness to subsequent stressors.

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