OBJECTIVES: Lipodystrophy syndromes (LD-S) are rare syndromes characterized by selective loss of fat and severe metabolic abnormalities. Based on patient accounts, LD-S have a significant impact on quality of life (QOL). This is the initial organized effort to estimate the QOL for individuals with LD-S based on the patient’s self-reported findings. METHODS: LD Connect, launched in January 2014, is a global registry for the lipodystrophy community, including patients and caregivers. This registry collects self reported data from members who join the effort on the registry website (www.ldconnect.org). We analyzed QOL data collected from individuals who self-identified as having lipodystrophy through December 9, 2014. The QOL questionnaire included items from the Patient Reported Outcomes Measurement Information System (PROMIS) short forms,  questions on financial impact and impact of pain. We estimated T-scores for the participants where a T-score of 50 represents the average score for the general population with a standard deviation (SD) of 10. EQ-5D scores were also estimated from PROMIS global health items. RESULTS: Out of 126 participants, 48% responded to the QOL questionnaire. Among responders 97% were females, 84% had partial LD, and 51% were from the US. T-scores for physical and mental health were 43.14 and 41.90 (SD 9.05 and 9.38, respectively). T-scores for social isolation, social support, and stigma were 51.57, 52.91, and 55.30, respectively. The estimated average EQ-5D score for LD-S was 0.67; much lower than the average EQ-5D of a general population (0.866). Patients also reported a minimal to moderate financial impact of lipodystrophy, with 27% reporting that costs affected their decision to seek care for lipodystrophy. CONCLUSIONS: LD-S patients reported having some impairment in quality of life on domains of physical health, and mental health, social isolation, and stigma compared to general population. Further work is required to characterize the extent of impairment.