Liberal oxygen therapy has been a cornerstone in the treatment of critically ill patients. Recently, awareness of hyperoxia toxicity has emerged. We investigated the partial pressure of oxygen in arterial blood (PaO2) in sepsis patients admitted to the emergency department treated with a reduced inspired oxygen fraction of 0.4 instead of 0.6–0.8. A prospective pilot study was carried out over a 3-month period. Patients admitted with two or more SIRS criteria and a suspicion of infection were included. They received 10 l O2/min through a VentiMask 40%. Of 83 patients, 77 had a PaO2 greater than 9.5 kPa with 10 l O2/min, of whom 51 had hyperoxia. Six patients showed hypoxia with 10 l O2/min. Of the hyperoxic patients, 8% died in hospital versus 6% with normoxia. Less than 8% of patients had hypoxia with 10 l O2/min; 66% were hyperoxic. Titration of oxygen therapy to normoxia in the emergency department should be evaluated.