A meta-analysis assessed the effect of combining continuous positive airway pressure (CPAP) with lifestyle interventions in patients with obstructive sleep apnea (OSA). It included 14 randomized controlled trials with 1623 patients. The combination treatment significantly reduced the apnea-hypopnea index (AHI) by mean differences MD = -9.99 (95% CI: -14.55 to -5.44, p < 0.001), with moderate quality GRADE evidence. AHI reductions were greater in multicomponent interventions (diet, exercise, behavioral strategies; MD = -11.99, p < 0.001, GRADE: moderate), interventions of less than 12 weeks (MD = -19.29, p < 0.001, GRADE: low to moderate) and reductions in BMI ≥ 5 kg/m² (MD = -23.39, p < 0.001, GRADE: low). Meta-regression showed that older age was associated with a greater reduction in AHI (β = -1.12, p = 0.024). Evidence is limited by high heterogeneity and risk of publication bias.