Background <p>Weight loss in light of various weight management strategies, including bariatric surgery, is recognized to vary according to sex.</p> Objectives <p>This study aimed to compare sex differences in adiposity phenotypes, body fat mobilization, and obesity-associated comorbidities at baseline and after bariatric surgery.</p> Methods <p>Ninety patients (26 men and 64 women) who underwent biliopancreatic diversion with duodenal switch surgery (BPD-DS) were included. Medical history, anthropometric, and bioelectrical impedance measurements as well as computed tomography scans (CT scan) were performed at baseline and at 12-month after BPD-DS. Sex differences in post-operative fat and muscle mobilization were assessed using one-way analysis of variance.</p> Results <p>At baseline, men (mean age 44.5 ± 13.2&#xa0;years) presented a higher global lean mass, abdominal muscle (estimated using CT scan), a higher volume of abdominal visceral fat, and a larger proportion of mid-thigh muscle infiltrated with lipids; a proxy for ectopic fat deposition in skeletal muscle compared to women (<i>p</i> &lt; 0.05 for all). After BPD-DS, there were no differences in fat distribution between sexes, except for abdominal fat volume and muscle infiltrated with lipids which remained higher in men (<i>p</i> &lt; 0.05). These differences translated into a numerically non-significant lower rate of remission of comorbidities in men.</p> Conclusions <p>Our result reports on sex differences in body fat mobilization at 12&#xa0;months post-BPD-DS. Despite comparable body mass index and overall lean and fat mass, men exhibit a higher volume of abdominal fat volume and greater ectopic fat deposition in skeletal muscles compared to women.</p>