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<b>Background:</b> Little is known about the role of rehabilitation medicine in obesity. <b>Objective:</b> to examine the benefits of a multidisciplinary rehabilitation program on the quality of life in patients with severe obesity. <b>Methodology:</b> We included 124 patients with obesity (mean age: 57 years; BMI ≥30), in an 8-week in-hospital multidisciplinary supervised program combining physiotherapy, nutrition and psychological support. Clinical, bio-psychological and functional parameters, as well as an obesity-specific quality-of-life score, were acquired at 0 and 8 weeks. <b>Results:</b> The quality-of-life score improved significantly at 8 weeks, from 60.8 to 68.8 (<i>p</i> < 0.0001), and was positively correlated with cardio-respiratory function (r = 0.47; <i>p</i> < 0.0001). <b>Conclusions:</b> Our results highlight the important role of multidisciplinary rehabilitation medicine and its integrated approach to improve the quality of life of people with obesity.