Obstructive sleep apnea occurs frequently in patients with drug-resistant hypertension. The factors accounting for this observation, however, are unclear. Both conditions demonstrate clinical features suggestive of extracellular fluid volume overload. The aims of this study were to examine whether the spontaneous overnight fluid shift from the legs to the upper body is associated with obstructive sleep apnea in hypertensive subjects and whether its magnitude is greater in drug-resistant hypertension. Leg fluid volume and the circumference of the calf and neck were measured before and after sleep in drug-resistant hypertensive (n = 25) and controlled hypertensive (n=15) subjects undergoing overnight polysomnography. The severity of obstructive sleep apnea was greater in the drug-resistant hypertensive group than in the controlled hypertensive group (apnea-hypopnea index: 43.0 ± 5.4 versus 18.1 ± 4.2 events per hour of sleep; P = 0.02, case-mix adjusted). In both groups, the apnea-hypopnea index strongly related to the amount of leg fluid volume displaced (R² = 0.56; P < 0.0001), although the magnitude of change was greater in the drug-resistant hypertensive group (346.7 ± 24.1 versus 175.8 ± 31.3 mL; P = 0.01, propensity-score adjusted). The overnight reduction in calf circumference and increase in neck circumference were also greater in drug-resistant hypertension (both P ≤ 0.02). In hypertensive subjects, rostral fluid displacement strongly relates to the severity of obstructive sleep apnea with its magnitude being greater in drug-resistant hypertension. Our findings support the concept that fluid redistribution centrally during sleep accounts for the high prevalence of obstructive sleep apnea in drug-resistant hypertension.