OBJECTIVES: The link between obesity or being overweight with life-threatening illnesses is well established. Furthermore, health-related quality of life (HRQoL) is reduced when body mass index (BMI) is elevated, but there are limited data on the effects of BMI on HRQoL in the general population or the aspects of HRQoL that are most affected. The objective of this study was to investigate the relationship between BMI and HRQoL, and any differences between men and women using data from the 2003 Health Survey of England. METHODS: HRQoL (derived from EQ-5D responses) data from the 2003 Health Survey of England was used. Responses from 14,836 individuals were utilised, and univariate regression and linear regression analyses, controlling for confounding factors such as obesity related co-morbidities, were conducted to examine the relationship between BMI and HRQoL. RESULTS: A significant association between BMI and HRQoL was found after controlling for gender, age, age when left school, manual work, and five obesity-related morbidities. The maximum HRQoL was reached at a BMI of 26.0 in males and at a BMI of 24.4 in females, which means that BMI is negatively associated with HRQoL for both underweight and obese individuals. At higher BMI values, men reported higher HRQoL than women, suggesting that obesity and being overweight has a greater impact on HRQoL for females than for males. At lower BMI values, HRQoL was lower in men than women. In women, all five dimensions of the EQ-5D (mobility, self-care, usual activity, pain and anxiety) worsened with obesity – in men, all but anxiety were worsened. CONCLUSIONS: There is a significant association between BMI and HRQoL in males and females in the general population. Nearly all aspects of HRQoL are adversely affected by elevated BMI. The optimum HRQoL is achieved with a BMI of approximately 25 for both males and females.