Background: The impact of overweight and nonmorbid obesity on health-related quality of life (HRQL) has not been widely researched. The aim of this study was to evaluate the effects of a lifestyle modification program (LMP) focused on diet, exercise, and psychological support on HRQL in overweight and nonmorbidly obese patients treated in a primary healthcare setting. Methods: Sixty patients with grade II overweight and nonmorbid grade I-II obesity were included in this open pilot clinical trial; subjects' ages ranged from 18 to 50 years. They were provided with an LMP combining nutrition education, physical activity, and psychological support. Subjects attended group sessions every 2 weeks. The main outcome measures at baseline and 6 months were body composition parameters (body mass index, body fat percentage, and waist circumference) and HRQL using the 1.4 Spanish version of the SF-36 questionnaire. The questionnaire yields an 8-scale profile of physical functioning (PF), role-physical (RP), bodily pain (BP), vitality (VT), social functioning (SF), role-emotional (RE), mental health (MH), and general health (GH) factors. Results: The LMP achieved improvements in SF-36 subscales at the end of the intervention: PF (80.37 +/- 18.90 vs 89.40 +/- 13.95, P < .001), RP (20.37 +/- 9.10 vs 23.14 +/- 6.67, P < .05), VT (58.71 +/- 21.98 vs 70.91 +/- 26.56, P < .01), SF (79.62 +/- 27.76 vs 86.57 +/- 25.45, P < .03), and GH (61.03 +/- 19.13 vs 69.42 +/- 18.80, P < .001). Conclusion: An LMP focused on balanced and moderate energy-restricted diets, increased physical activity, and psychological support may improve the anthropometric parameters and the quality of life in moderately obese patients treated in a primary healthcare center. (Nutr Clin Pract. 2011;26:316-321)