PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear. METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.