Previous studies show that prolonged exposure to a high inspired oxygen concentration (FiO 2) is associated with unfavourable haemodynamic effects. Until now, it is unknown if similar effects also occur after oxygen therapy of limited duration in the emergency department (ED). Objectives To investigate the haemodynamic effects of a high FiO 2 administered for a limited duration of time in patients who receive preoxygenation for procedural sedation and analgesia (PSA) in the ED. Design, settings and participants In a prospective cohort study, cardiac output (CO), stroke volume (SV) and systemic vascular resistance (SVR) were measured using the Clearsight non-invasive CO monitoring system in patients who received preoxygenation for PSA in the ED. Measurements were performed at baseline, after 5 min of preoxygenation via a non-rebreathing mask at 15 /L min and after 5 min of flush rate oxygen administration. Outcomes measures The primary outcome was defined as the change in CO (L/min) from baseline after subsequent preoxygenation with 15 L/min and flush rate. Results Sixty patients were included. Mean CO at baseline was 6.5 (6.0-6.9) L/min and decreased to 6.3 (5.8-6.8) L/min after 5 min of oxygen administration at a rate of 15 L/min, and to 6.2 (5.7-6.70) L/min after another 5 min at flush rate (p=0.037). Mean SV remained relatively constant during this period, whereas mean SVR increased markedly (from 781 (649-1067), to 1244 (936-1695) to 1337 (988-1738) dyn/s/cm -5, p<0.001. Sixteen (27%) patients experienced a>10% decrease in CO. Conclusion Exposure of patients to a high FiO 2 for 5-10 min results in a significant drop in CO in one out of four patients. Therefore, even in the ED and in prehospital care, where oxygen is administered for a limited amount of time, FiO 2 should be titrated based on deficit whenever this is feasible and high flow oxygen should not be given as a routine treatment.