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Background: Coronavirus disease 2019 (COVID-19) infection is associated with significant morbidity and mortality. Some patients develop severe acute respiratory distress syndrome and kidney failure requiring the combination of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Methods: Retrospective cohort study of 127 consecutive patients requiring combined ECMO and CRRT support in intensive care units at an ECMO center in Marietta, GA, United States. Results: Sixty and 67 patients with and without COVID-19, respectively, required ECMO-CRRT support. After adjusting for confounding variables, patients with COVID-19 had increased mortality at 30 days (hazard ratio [HR], 5.19; 95% confidence interval [CI], 2.51–10.7; P<0.001) and 90 days (HR, 6.23; 95% CI, 2.60–14.9; P<0.001). Conclusions: In this retrospective study, patients with COVID-19 who required ECMO-CRRT had increased mortality when compared to patients without COVID-19.