Background: Psychological dimensions (i.e. low self-esteem) frequently accompany psychiatric disorders and also play some role in quality of life for psychiatric patients. Emotional fragility (EF) is a personality trait consisting of the tendency to experience feelings of discomfort, self-inadequacy, vulnerability, irritability, emotional instability, and self-blame. Very few studies address the role of EF for psychiatric patients. Objective: The objective of this study was to investigate the relationship between EF and perceived well-being in psychiatric patients. Methods: 70 in-patients of a psychiatric clinic consented to participate in the study. All of them were women, mean aged 51 ±14 years, diagnosed, according to DSM IV criteria, as follows: 38 mood disorders (10 unipolar depression, 12 reactive depression, 16 major depression), 5 anxiety disorders, 14 schizofrenia/psychotic disorders, and 12 substance-related disorders. All patients completed the Emotional Fragility Scale (EFs) and the Cognitive Behavioural Assessment-B Scale to measure perceived well-being, stress, and negative mood state. Results: The results of the present study demonstrate that all psychiatric patients suffer from lowered perceived well-being. Furthermore, the degree to which well-being was lowered differed among various diagnostic groups: it was lowest in patients with depressive disorders and substance abuse (p<0.03). Also, there is evidence of the predictive role of EF on symptoms of lowered well-being. After controlling for age, psychiatric diagnosis, and pharmacological treatment, EF predicted 28%* of poor well-being, 29%* of high perceived stress and 24%* of negative mood state, using multiple regression models (*p<0.0001). Conclusions: We conclude that there is an effect of Emotional Fragility on lowering the perceived well-being of psychiatric patients and this effect is more pronounced with certain psychiatric disorders, such as major depression and substance abuse. The results of this study may have implications for specific psychological interventions to integrate pharmacological treatment.