Objective: Exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation (ROSC), but its effects on neurological outcome are uncertain, and study results are inconsistent. Methods: Exploratory post hoc substudy of the Target Temperature Management (TTM) trial, including 939 patients after OHCA with return of spontaneous circulation (ROSC). The association between serial arterial partial pressures of oxygen (PaO ₂ ) during 37 h following ROSC and neurological outcome at 6 months, evaluated by Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5), was investigated. In our analyses, we tested the association of hyperoxemia and hypoxemia, time-weighted mean PaO ₂ , maximum PaO ₂ difference, and gradually increasing PaO ₂ levels (13.3-53.3 kPa) with poor neurological outcome. A subsequent analysis investigated the association between PaO ₂ and a biomarker of brain injury, peak serum Tau levels. Results: Eight hundred sixty-nine patients were eligible for analysis. Three hundred patients (35%) were exposed to hyperoxemia or hypoxemia at some time point after ROSC. Our analyses did not reveal a significant association between hyperoxemia, hypoxemia, time-weighted mean PaO ₂ exposure or maximum PaO ₂ difference and poor neurological outcome at 6-month follow-up after correction for co-variates (all analyses p = 0.146-0.847). We were not able to define a PaO ₂ level significantly associated with the onset of poor neurological outcome. Peak serum Tau levels at either 48 or 72 h after ROSC were not associated with PaO ₂ . Conclusion: Hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first 37 h of hospitalization and was not significantly associated with poor neurological outcome after 6 months or with the peak s-Tau levels at either 48 or 72 h after ROSC.