The aim was to assess dimensions of health-related quality of life (HRQL) in women attending an obesity clinic, and to rate differences in HRQL in those with the highest and lowest levels of physical activity (PA). The sample included 113 sedentary and 101 physically active subjects from a total sample of 375 overweight women 16–65 years, with a body mass index (BMI) ≥27.5 kg/m2 consulting at an outpatient Endocrinology Clinic, and 82 lean female volunteers who served as a reference. Weight, height, body composition, PA, physical medical conditions, depression, body image, cognitive-behavioral conceptualization of obesity, eating behavior, functional status, walking ability, exercise capacity, social functioning, and general health and perceived quality of life were assessed cross-sectionally. The prevalence of medical conditions and depression was not statistically different (P<0.05) in sedentary and active women. In sedentary obese women, body attitude, walking ability, and aerobic fitness were poorer; the number of people to turn to for social support was smaller; physical attributions about the basis of the subjects obesity were less pronounced; and eating was more the consequence of external triggers or diffuse emotions than in physically active obese women (P<0.05). The findings indicate that a higher level of PA in an obese female clinical population was positively associated with diverse dimensions of HRQL. However, it was not possible to determine if these favorable aspects of HRQL are the cause or the consequence of a higher PA level. Am. J. Hum. Biol. 14:777–785, 2002. © 2002 Wiley-Liss, Inc.