High oxygen concentration in blood may be harmful in the reperfusion phase after cardiopulmonary resuscitation. We compared the effect of 30 and 100% inspired oxygen concentrations on blood oxygenation and the level of serum markers (NSE, S-100) of neuronal injury during the early post-resuscitation period in humans.Patients resuscitated from witnessed out-of-hospital ventricular fibrillation were randomised after the return of spontaneous circulation (ROSC) to be ventilated either with 30% (group A) or 100% (group B) oxygen for 60min. Main outcome measures were NSE and S-100 levels at 24 and 48h after ROSC, the adequacy of oxygenation at 10 and 60min after ROSC and, in group A, the need to raise FiO 2 to avoid hypoxaemia. Blood oxygen saturation <95% was the threshold for this intervention.Thirty-two patients were randomised and 28 (14 in group A and 14 in group B) remained eligible for the final analysis. The mean PaO 2 at 10min was 21.1kPa in group A and 49.7kPa in group B. The corresponding values at 60min were 14.6 and 46.5kPa. PaO 2 values did not fall to the hypoxaemic level in group A. In another group FiO 2 had to be raised in five cases (36%) but in two cases it was returned to 0.30 rapidly. The mean NSE at 24 and 48h was 10.9 and 14.2μg/l in group A and 13.0 and 18.6μg/l in group B (ns). S-100 at corresponding time points was 0.21 and 0.23μg/l in group A and 0.73 and 0.49μg/l in group B (ns). In the subgroup not treated with therapeutic hypothermia in hospital NSE at 24h was higher in group B (mean 7.6 versus 13.5μg/l, p=0.0487).Most patients had acceptable arterial oxygenation when ventilated with 30% oxygen during the immediate post-resuscitation period. There was no indication that 30% oxygen with SpO 2 monitoring and oxygen backup to avoid SpO 2 <95% did worse that the group receiving 100% oxygen. The use of 100% oxygen was associated with increased level of NSE at 24h in patients not treated with therapeutic hypothermia. The clinical significance of this finding is unknown and an outcome-powered study is feasible.