People with eating disorders show impaired health-related quality of life (HRQoL). We aimed to investigate the relative role of physical and mental factors and stage of change as possible predictors of HRQoL in a group of Spanish women (n = 124) with eating disorders. For this purpose, initial and follow-up data were obtained after 6 months from patients attending an outpatient treatment unit for eating disorders. The determinants of the physical and mental domains of the Medical Outcomes Survey Short-form Health Survey (SF-36) questionnaire were investigated in the total sample and separately based on the eating disorder diagnosis by multiple linear regression. Lower scores in the physical component of the SF-36 questionnaire were associated with the presence of a higher body mass index (BMI) at follow-up as well as a higher score in the "action" component of the Attitudes towards Change in Eating Disorders Questionnaire (ACTA). Conversely, a higher index in the EuroQoL-5D overall quality of life questionnaire (EQ-5D) and the presence of obsessive compulsive disorder were associated with a higher score in the physical dimension. The instrument used demonstrated the ability to assess changes associated with the physical component of these patients over the period studied, and the analysis provided more information and specific data on different aspects of HRQoL, thus allowing a more detailed analysis of the information.