During refractory cardiogenic shock and cardiac arrest, veno‑arterial extracorporeal membrane oxygenation (VA‑ECMO) is used to restore a circulatory output. However, it also impacts significantly arterial oxygenation. Recentguidelines of the Extracorporeal Life Support Organization (ELSO) recommend targeting postoxygenator partialpressure of oxygen (PPOSTO2 ) around 150 mmHg. In this narrative review, we intend to summarize the rationale andevidence for this P POSTO2 target recommendation. Because this is the most used configuration, we focus on peripheralVA‑ECMO. To date, clinicians do not know how to set the sweep gas oxygen fraction (F S O2). Because of the oxy‑genator’s performance, arterial hyperoxemia is common during VA‑ECMO support. Interpretation of oxygenation iscomplex in this setting because of the dual circulation phenomenon, depending on both the native cardiac outputand the VA‑ECMO blood flow. Such dual circulation results in dual oxygenation, with heterogeneous oxygen partialpressure (PO 2) along the aorta, and heterogeneous oxygenation between organs, depending on the mixing zonelocation. Data regarding oxygenation during VA‑ECMO are scarce, but several observational studies have reported anassociation between hyperoxemia and mortality, especially after refractory cardiac arrest. While hyperoxemia shouldbe avoided, there are also more and more studies in non‑ECMO patients suggesting the harm of a too restrictiveoxygenation strategy. Finally, setting F S O2 to target strict normoxemia is challenging because continuous monitoringof postoxygenator oxygen saturation is not widely available. The threshold of P POSTO2 around 150 mmHg is supportedby limited evidence but aims at respecting a safe margin, avoiding both hypoxemia and severe hyperoxemia.