Diuretics have been reported as effective for reducing obstructive sleep apnea (OSA) severity by preventing fluid retention and reducing rostral fluid shift. The benefit of diuretics might vary depending upon the OSA clinical phenotype and comorbidities. To test this hypothesis, we conducted a propensity score-matched cohort analysis of data from the French national sleep apnea registry "Observatoire Sommeil de la Fdration de Pneumologie" (OSFP).A propensity score analysis was used to determine the impact of diuretics on OSA severity. Matching (ratio 1:4) was performed by using a 0.1 collider for the propensity score. Severe OSA was defined as an apnea-hypopnea index (AHI) > 30 events/h and the usefulness of diuretics was assessed using a logistic regression model.The 69,564 OSA patients studied in the OSFP prospective observational cohort had a median age of 56.9 years [Interquartile range (IQR): 47.4; 65.6], 67% were men, and the median AHI was 28 [14; 43] events/h. Among them, 9,783 (14.1%) were treated with diuretics. Diuretics reduced OSA severity in overweight or moderately obese patients (p=0.03) and in patients with hypertension (p<0.01), particularly in hypertensives with a body mass index between 25 and 35 kg/m2 (p<0.01). Diuretics had no significant effect on OSA severity in patients with self-reported low physical activity or heart failure.Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined therapies for hypertensive patients with OSA.