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Abstract: In patients on veno-arterial extracorporeal membrane oxygenation (ECMO) premembranous venous oxygen saturation (Spm-vO2) is continuously displayed on the ECMO console. However, the concordance between Spm-vO2 and mixed venous oxygen saturation (SvO2) remains largely unexplored. Our single-center retrospective study included adult patients who had paired SvO2 and Spm-vO2 readings within 15 minutes of each other, on peripherally cannulated Vf ivc-A ECMO and a pulmonary artery using catheter (PAC). The 82 pairs of observations showed a mean difference of 11.37% (95% limits of agreement −6.0 to 28.74, p < 0.001) between Spm-vO2 and SvO2. Although the two values correlated with each other (r = 0.51, p < 0.01), the difference between the paired measurements was larger at lower values of SvO2 (3.72 ± 6.38% when SvO2 >80%, 11.79±7.46% when SvO2 between 60% and 80%, and 18.81±12.09% when SvO2 <60%). The equation SvO2 = 1.2* Spm-vO2 – 28.03 was obtained by Passing Bablok regression. Cardiac index calculated by Spm-vO2 and SvO2 differed by 0.8L/minute/m2 (95% limits of agreement −0.52 to 2.17, p < 0.001). In peripheral VA-ECMO, Spm-vO2 is consistently higher than SvO2, with more discordance at lower saturation levels. Using Spm-vO2 to estimate cardiac output using Fick method yields inaccurate results.