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Increasingly compelling data link chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) to cardiovascular complications independent of known comorbidities. It remains unclear whether the association is amplified in the presence of both conditions. The aims of this study are to assess the prevalence of atrial fibrillation (AF) in overlap syndrome (OS) and to identify risk factors predisposing to this atrial arrhythmia. We conducted a retrospective cohort study of 268 adults without past or current AF who were referred for an initial diagnostic polysomnogram from 2012 to 2019. A logistic regression analysis was performed to identify risk factors for incident AF. Incident AF occurred in 64 subjects [cumulative probability 24%, 95% confidence interval (CI) 19-29]. Independent predictors of incident AF were age-adjusted Charlson index [Odds ratio (OR) 1.62; 95% confidence interval (CI) 1.3-2.0], percentage of time spent with O 2 saturation below 90% (CT90) (OR 3.72, 95% CI 1.18-11.71), and CPAP adherence (OR 0.32, 95% CI 0.13-0.71). OS patients with AF experienced higher hospitalization rates (OR 1.25, 95% CI 1.03-2.37) and worse mortality rates (OR 1.92, 95% CI 1.04-3.54). In multivariate Cox proportional regression, age-adjusted Charlson Index, severity of airflow obstruction, and CPAP adherence were independent predictors of mortality. The burden of hypoxemia and severity of comorbidities are independent factors for incident AF in individuals with OS. CPAP adherence may mitigate the risk of AF and reduce the rate of mortality in this population.