Obesity is a major risk factor for obstructive sleep apnoea (OSA), the most common sleep-disordered breathing related to neurocognitive and metabolic syndromes, type II diabetes, and cardiovascular diseases. Although strongly recommended for this condition, there are no studies on the effectiveness of an interdisciplinary weight loss and lifestyle intervention including nutrition, exercise, sleep hygiene, and smoking and alcohol cessation. INTERAPNEA is a randomised controlled trial with a two-arm parallel design aimed at determining the effects of an interdisciplinary tailored weight loss and lifestyle intervention on OSA outcomes. The study will include 84 males aged 18–65 with a body mass index of ≥25 kg/m2 and severe to moderate OSA randomly assigned to usual care (i.e., continuous positive airway pressure), or interdisciplinary weight loss and lifestyle intervention combined with usual care. Outcomes will be measured at baseline, intervention end-point, and six-month post-intervention, including apnoea-hypopnoea index (primary outcome), other neurophysical and cardiorespiratory polysomnographic outcomes, sleep quality, daily functioning and mood, body weight and composition, physical fitness, blood biomarkers, health-related quality of life, and cost-effectiveness. INTERAPNEA may serve to establish a cost-effective treatment not only for the improvement of OSA and its vast and severe comorbidities, but also for a potential remission of this condition.