Background: The aims of this study were 1) to examine potential sex-related differences in major cardiometabolic risk factors among severe/morbid obese (body mass index [BMI] >= 35) individuals; 2) to assess whether severity of obesity is associated with more adverse cardiometabolic risk factors in women and men, and 3) to assess whether being physically active (>= 500 metabolic equivalents [MET-minutes per week]) may play a role in the association between severity of obesity and the cardiometabolic risk profile. Methods: A total of 886 (438men) obese individuals participated in a population-based cross-sectional study. We categorized participants as grade I (BMI 30-34.99) and grade II/III (BMI >= 35) obese. We measured markers of lipid and glucose metabolism, inflammation (high sensitivity C-reactive protein [hs-CRP]) blood pressure and renal function, as well as self-reported physical activity. Results: Triglycerides, insulin, HOMA-IR, systolic blood pressure and creatinine levels were higher in severe/morbid obese men than women (all, P <0.05), while women presented higher HDL cholesterol and hs-CRP (P <0.05) than men. Severe/morbid obesity was associated with higher triglycerides, hs-CRP, insulin and insulin resistance, diastolic blood pressure and higher odds of hypertension than grade I obesity both in women and men (all, P <0.05). Severe/morbid obese individuals who were physically inactive presented the least favorable cardiometabolic profile (P <0.05). Conclusions: Severe/morbid obesity is associated with more adverse cardiometabolic risk factors both in women and men. Severe/morbid obese men are more affected than women regarding their cardiometabolic profile, although women presented higher inflammation. Physically inactive individuals with severe/morbid obesity had the most adverse clustered cardiometabolic risk profile. (C) 2016 Elsevier Ireland Ltd. All rights reserved.