Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 6-20% of reproductive aged women worldwide. It is commonly described as a significant genetic, hormonal, metabolic, and reproductive disorder. Women with PCOS were found to have higher levels of anxiety and depression, which may impact negatively on their health-related quality of life (HRQOL). Objective: To explore the relationship between psychological distress and health-related quality of life among women with polycystic ovary syndrome. Setting: The study was carried out at outpatient gynecology clinics of EL-Shatby Maternity University Hospital in Alexandria, Egypt. Subjects: A convenient sample of 120 women with PCOS aged between 18-45 years, was selected from the aforementioned setting. Tools: three tools were used. Tool one: “A socio-demographic, Reproductive and clinical data structured interview schedule ". Tool two: “The Modified Polycystic Ovary Syndrome Questionnaire (MPCOSQ)". Tool three:" Kessler Psychological Distress Scale (K10)." Results: The study showed that slightly less than three-quarters (71.7%) of the studied subjects had severe mental distress, slightly more than one-half (51.7%) had moderate level of HRQOL. While 45.8% of them had low level of HRQOL. A highly statistically significant negative correlation between the total score of psychological distress of the studied subjects and their total score of health-related quality of life was found, where r= –0.465* and p <0.001*. Conclusion: Psychological distress is negatively correlated with health-related quality of life (HRQOL) among women with polycystic ovary syndrome (PCOS), with emphasis on emotional problems, infertility, menstrual symptoms and menstrual predictability domains. Recommendations: Clinical staff including nurses should consider potential psychosocial problems when caring for patients with PCOS, not only the physical symptoms. Include evaluation of HRQOL in the assessment tool on patients' admission. Enhancing HRQOL may be part of nursing process. Developing periodical workshops to increase nurses' awareness about causes, risk factors, physical symptoms, psychological effects as well as, the relation between psychological distress and HRQOL. Designing individualized care plans which include women's concerns related to underlying endocrine imbalances, nutritional counselling, treating skin and hirsutism, and pursuing fertility treatment if desired. Implementing health/psycho-education programs for women with PCOS about causes, psychological and physical symptoms, management, counselling sessions, as well as psychiatric assistance in severe psychological suffer.