OBJECTIVES: To determine the relationship between diabetes symptom burden and patients' perceptions of health-related quality of life (HRQL). METHODS: A questionnaire was sent to 3,716 adults with diabetes enrolled in a managed care organization in West Virginia and southeastern Ohio. Diabetes symptom burden was measured using a 17-item scale (Diabetes TyPE, Form 2.1). The Health Status Questionaire (HSQ-12), Version 3.0 was utilized to measure patients' perception of their HRQL. Analyses focused on six domains from the HSQ-12: General Health Perception (GHP), Physical Functioning (PF), Bodily Pain (BP), Energy/Fatigue (EF), Social Functioning (SF), and Mental Health (MH). Linear regression was used to examine the impact of diabetes symptoms on each of the HRQL domains. RESULTS: Usable responses were obtained from 1,027 persons with diabetes (27.6% response rate). The summated scale of diabetes symptom burden had acceptable internal consistency (alpha=0.90). Analyses revealed a significant inverse relationship between diabetes symptom burden and each of the six domains from the HSQ-12, when controlling for gender, age, and education. Overall symptom burden was found to be most highly associated with Social Functioning (r=-.57), while somewhat less strongly associated with the other five domains: GHP (r=-.52); PF (r=-.49); BP (r=-.51); EF (r=-.54); MH (r=-.50). As overall symptom burden increases, the patients' perception of health across all six HRQL domains decreases. CONCLUSIONS: Diabetes symptom burden is inversely related to health-related quality of life. Thus, interventions targeted towards the alleviation of diabetes symptoms should also lead to improvements in patients' perceptions of their health and well-being.