Mortality in patients treated with extracorporeal membrane oxygenation (ECMO) is high. Therefore, it is crucial to better understand conditions that are associated with mortality in ECMO patients. In this retrospective analysis, we observed 51 patients treated with high-flow ECMO in 2013 and 2014 at our center. We recorded laboratory values and intensive care procedures. The hypothesis of bilirubin being a predictor of mortality during ECMO treatment was initially addressed. Therefore, laboratory values were obtained before initiation and at the time of highest bilirubin throughout the procedure. Receiver operating characteristic (ROC) curves and survival analysis were conducted. Our cohort consisted of patients with advanced age (median: 55 years; range: 22–76) and high mortality (26/51; 51%). Lactate, bilirubin, and NT-pro-BNP were significantly (p < 0.05) associated with mortality in univariable analyses. The cut-off values with highest Youden’s index were bilirubin ≥10 mg/dl, lactate ≥2.25 mmol/L, and NT-pro-BNP ≥11,500 pg/ml. A multivariable analysis, revealed an area under the curve (AUC) of 0.85 (95% confidence interval [CI]: 0.74–0.97), sensitivity of 0.79, and specificity of 0.91. Bilirubin, lactate, and NT-pro-BNP were associated with mortality during ECMO treatment. However, laboratory values were only evaluated at the time of peak bilirubin.