Background: In social neuroscience, the linkage between the endocrinological system and the etiology and symptomatology of mental health problems has received increasing attention. A particular focus is given to the neuropeptide oxytocin with its anxiolytic and stress-buffering effect and the resulting therapeutic potential for anxiety disorders. Even though anxiety disorders are the most prevalent mental health disorders in childhood and adolescence worldwide, the reactivity of the endogenous oxytocin system to an acute stressor (Trier Social Stress Test, TSST) has so far only been investigated in healthy children. It has been shown that peripheral oxytocin levels increased under psychosocial stress conditions. In the present study, it is hypothesized that the endogenous oxytocin system in children and adolescents suffering from a clinically diagnosed anxiety disorder is dysregulated. Three primary outcome parameters will be analyzed: significant differences between participants with anxiety disorders compared to healthy controls in basal oxytocin levels, varying salivary oxytocin release after stress exposure and the correlation between the cortisol peak/-decrease and oxytocin level over time. Secondary outcome criteria are significant differences in physiological (heart rate) and psychological (perceived stress, anxiety, insecurity, tension) responses. Methods: The present study is a single-center experimental observation study to investigate the reactivity of the endocrinological system to a psychosocial stressor (TSST). 32 children and adolescents (11-18 years) suffering from anxiety disorder will be compared to a matched healthy control group. After a detailed psychological assessment, saliva samples will be taken to measure oxytocin levels before and after psychosocial stress exposure at eight different time points. Additionally, the stress hormone cortisol will be analyzed according to the same procedure. Discussion: Due to the high prevalence and comorbidity rate with numerous other psychiatric disorders and mental health problems, there is an urgent need to strengthen research in possible neurobiological underpinnings of anxiety disorders. To our knowledge, the proposed experiment is the first study to examine the endocrinological oxytocin and cortisol reaction to an acute psychosocial stressor in children and adolescents with mental health disorders.