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Qing Liu,1,2 Wenjuan Zhang3 1College of Education and Technology, Zhejiang University of Technology, Hangzhou, People’s Republic of China; 2School of Psychology, Beijing Normal University, Beijing, People’s Republic of China; 3Mental Health Education Center, Xidian University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Qing LiuZhejiang University of Technology Hangzhou, 310014, People’s Republic of ChinaTel/Fax +86 571 85290114Email 0616566@zju.edu.cnObjective: The aims of the present study were twofold: 1) to examine the effects of a virtual reality version of Trier Social Stress Test (TSST-VR) using a placebo as the control condition; 2) to delineate sex differences in psychophysiological responses following the TSST-VR.Methods: Healthy young male (n = 30) and female (n = 30) undergraduates were randomly assigned to a psychosocial stress protocol condition or to a non-stressful control condition (placebo) also under virtual reality environment (VR). Electrodermal activity (EDA), heart rate (HR) and heart rate variability (HRV) were measured throughout the condition. The visual analog scale (VAS) was used to assess the perceived stress before and after the condition. We also included subjective scales of emotional states and coping.Results: Different ANOVAs showed that after VR, the stress group reported higher scores on VAS than the non-stress group. Before VR, compared with females, the males showed stronger EDA and higher HRV. Under VR, the males had lower HR. After VR, the males’ HR was still lower than females’, but their HRV was higher than females’. Finally, the correlation between subjective and objective reactivity demonstrated that HRV during the experiment was negatively correlated to depression and negative affect. The HRV after VR was negatively correlated to the positive coping but was positively correlated to the depression.Conclusion: These findings suggest that the TSST-VR could be used as an available tool for testing sex differences to psychosocial stress induction in experimental settings. Compared with females, males were more sensitive to stress. The scores on depression, negative affect and positive coping before the stress induction may be able to predict the arousal of the sympathetic nervous system across the stress situations.Keywords: Trier Social Stress Test, virtual reality, placebo version, sex difference, stress reactivity, visual analog scale