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BACKGROUND: Recent studies have consistently shown that patients with lipedema are at a higher risk for depression and anxiety. The aim of this study is to identify the psychological factors associated with lipedema syndrome (LS) and their link to the patient's psychological symptomatology. METHODS: A mixed-methods approach was employed, combining quantitative and qualitative components. The quantitative component involved anonymous online questionnaires, including a Health and Demographic Questionnaire, the body satisfaction and global self-perception questionnaire (BSGSPQ), the lymphedema quality of life questionnaire (LYMQOL), and the Hospital Anxiety and Depression Scale (HADS). The qualitative component consisted of oral interviews to explore the complexity of the phenomenon. Participants included those with "easy bruising," a waist-to-hip ratio ≤0.7 (W/H), and pain levels ≥4/10 on the visual analogue scale (VAS). RESULTS: Our findings indicate that the level of depression is positively correlated with spontaneous pain (p = 0.002; r = 0.331) and the lack of medical understanding (p = 0.011; r = 0.229). Anxiety scores are inversely correlated with body satisfaction (r = -0.317) and global self-perception (r = -0.393); similarly, depression scores show similar correlations with body satisfaction (r = -0.445) and global self-perception (r = -0.608), all with p value of <0.0001. DISCUSSION AND CONCLUSION: This study highlights significant connections between the physical symptoms and mental health in patients with LS. The more affected the self-perception, the greater the depression and anxiety levels. These multiple contributing factors may explain the decline in quality of life (QOL) and deterioration of mental health. It is therefore crucial to proactively integrate mental health management into the care of LS patients. Future research should focus on identifying concrete, actionable methods to support women experiencing LS.