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BACKGROUND Metabolically healthy obesity (MHO) has been associated with lower risk of diabetes than obesity with cardiometabolic abnormalities (CA). However, the effect of MHO on other health outcomes is unknown. OBJECTIVE To examine the association of metabolic status across categories of body mass index (BMI) with health-related quality of life (HRQL). METHODS Prospective cohort with 4397 individuals aged ≥18 years, recruited in 2008-2010 and followed-up to 2012 in Spain. Normal weight was defined as BMI <25, overweight as BMI 25-29.9, and obesity as BMI ≥30 kg/m2. Two metabolic statuses were defined: healthy (0-1 CA) and unhealthy (≥2 CA). HRQL was measured with the physical component summary (PCS) and the mental component summary (MCS) of the SF-12 questionnaire. The association of joint categories of BMI and metabolic status at baseline with HRQL at 2012 was examined using linear regression, and adjusted for the main confounders. RESULTS Compared to healthy normal-weight subjects, the unhealthy normal-weight and the healthy overweight individuals had a similar PCS score; however, the PCS was lower (worse) among those with unhealthy overweight (-1.79; 95% confidence interval [CI]: -2.66 to -0.94), with MHO (-1.45; 95% CI: -2.67 to -0.24) and unhealthy obesity (-1.97; 95% CI: -2.88 to -1.05). Being overweight or obese was not associated with the MCS score regardless of metabolic status. CONCLUSION Metabolically unhealthy overweight, as well as obesity regardless of metabolic status, showed a worse physical HRQL. These results suggest that both obesity and CA should be addressed to improve HRQL.