Objective: To explore the health-related quality of life and how this is associated with symptoms of depression, anxiety and stress, mediated by personality characteristics in women with Endometriosis Design: Quantitative, cross-sectional study Setting: Cyprus Population or Sample: 47 Cypriot women aged between 20-46 diagnosed with Endometriosis. Methods: Participants, after receiving information about the aims and objectives of the study consented to complete either online or face-to-face questionnaires. With the use of an online platform, volunteers completed three questionnaires. Main Outcome Measures: The psychometric tools used were the Endometriosis Health Profile-30, the Depression, Anxiety and Stress Scale-21 (DASS-21) and the International Personality Item Pool - Five Factor Model 50. Results: Significant effects of health-related quality of life on symptoms of anxiety and stress emerged. Symptoms of depression showed no significant effect. Neuroticism affected symptoms of anxiety and stress in an unexpected way, as high levels of Neuroticism predicted low levels of symptoms of depression, anxiety and stress. Also, Neuroticism acts as a mediating factor between health-related quality of life and symptoms of anxiety and stress. Conclusions: These results show how drastically Endometriosis can negatively affect the mental health and quality of life of women. Health-related quality of life affects symptoms of anxiety and stress, which brings upon new evidence to enhance the embodiment of psychological support in the treatment of Endometriosis.