Obesity is a chronic, progressive, multifactorial medical condition. It is known that obesity is associated with cardiovascular disease, metabolic disorders, degenerative joint disorders, and decreased health-related quality of life (HRQoL). In addition, there are socio-economic, gender, age, and racial differences in the population distribution of obesity. The extent to which HRQoL is impaired by obesity independent of associated chronic disease and known demographic risk factors is less well understood by nurses. A secondary analysis of the National Health Measurement Study (NHMS) was conducted to illustrate this relationship. Regression analyses were used to assess the association between body mass index (BMI) and HRQol. BMI was categorized as normal, overweight, obese, and morbidly obese. HRQoL was measured using the EQ-5D and EQ-VAS. After adjusting for chronic health conditions and demographic factors, lower HRQoL was observed as BMI category increased for both the EQ-5D, F = 40.49, 15 df, p < .001, and EQ-VAS, F = 35.5, 15 df, p < .001.