Introduction: Considering the provision of bolder social roles for women and the exposure of employed married women to multifaceted roles, paying attention to their psychological well-being is essential. Therefore, the current study was conducted to predict psychological well-being based on health anxiety and perceived stress with the mediating role of self-handicapping in employed married women. Methods: This is a correlational study. The statistical population of the study was all married women aged 20-60 years, working in the School of Nursing and Midwifery affiliated to Tehran University of Medical Sciences in 2018. A sample of 266 people were included to the study by the consensus sampling method. The data collection tools were questionnaires including sociodemographic data, the Ryff psychological well-being questionnaire, Cohen’ s perceived stress scale, health anxiety short form, and the self-handicapping scale. The data were analyzed using the SPSS software version 25 and the AMOS software version 24. In this study, in order to evaluate the validity, the external validity and factor validity indices were used, and to assess the reliability, the combined reliability indices and Cronbach's alpha coefficient were used. Results: The results showed that health anxiety, perceived stress, and self-handicapping predicted 48% of the variance of psychological well-being. Also, perceived stress and health anxiety predicted 43% of the variance of self-handicapping, thereby affecting psychological well-being. Finally, the effects of the independent variables on the dependent, positive and significant were considered significant (P < 0. 05). Conclusions: Given the negative impact of perceived stress, health anxiety, and self-handicapping on the psychological well-being of employed married women, and considering the importance of the health of employed women who play roles both in the family and in the workplace, it is recommended that relevant organizations provide appropriate programs to control aforementioned factors and other possible factors.