Mild hypoxia is common in patients with stroke, and associated with worse long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no benefit after acute stroke, but did not report compliance and the effect on oxygenation. The aim of this study was to assess the effect of routine low-flow oxygen supplementation on oxygen saturation (SpO 2 ) in patients with acute stroke.In all, 63 patients with normoxic stroke and no indications for oxygen treatment were randomized to 2 L/min oxygen supplementation via nasal cannulae overnight or to control (room air) within 72 hours of symptom onset. Additional oxygen was given at the discretion of the clinical team, if medically indicated. SpO 2 was assessed from 22:00 to 09:00 by pulse oximetry. Compliance with the trial treatment and sleep status were recorded by nursing staff.In all, 59 patients were confirmed to have had a stroke and available for overnight monitoring. Six (2 oxygen, 4 control) had no or insufficient oximetry data for analysis. The mean nocturnal SpO 2 was 2.5% higher in the oxygen group (n = 27) than in the control group (n = 26) (P < .001). More patients on oxygen than control subjects had SpO 2 greater than 90% throughout the night (59% v 23%). Patients on oxygen had fewer desaturations than control subjects (oxygen desaturation index 4%, 0.8 v 2.1) (P = .001). Oxygen was found to be in place as prescribed in 71%. Oxygen supplementation was not associated with insomnia or restlessness. No patient in either group was given oxygen for clinical indications.Nocturnal oxygen supplementation at a rate of 2 L/min increases the mean nocturnal SpO 2 by 2.5% and reduces the number of nocturnal desaturations in patients with acute stroke.