Obesity is a major public health problem associated with increased health risks, chronic pain, and decrements in functional health status and subjective well-being. To examine the impact of pain on Health-Related Quality-of-Life (HRQL), 312 consecutive persons seeking medically-supervised weight loss treatment completed a sociodemographic questionnaire, the Medical Outcomes Study Short-Form Health Survey (SF-36), and underwent a series of clinical evaluations. Forty-eight percent of the patients when asked to rate 'How much pain have you had in the last four weeks?' reported at least moderate pain in the four weeks prior to treatment. In analyses adjusted for sociodemographic factors, body-mass index (BMI) (kg/m2), and depression, obese patients reporting pain scored significantly lower on all SF-36 domains than those not reporting pain. Findings indicate that the pain itself is independently associated with impaired HRQL in nearly half of obese persons seeking treatment. These data demonstrate that pain is a strong covariate of obesity and, therefore, may need to be considered in the design and development of obesity treatments.