Background: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. About two-thirds of the severe cases may be rescued by extracorporeal membrane oxygenation (ECMO). However, about half of the patients supported by ECMO suffer major complications. High volume hemofiltration (HVHF) is a depurative extracorporeal support that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. Methods: We implemented HVHF prior to ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if ECMO was avoided and nonresponders if ECMO support was needed. Results: The first two patients required ECMO, while the last three did not. Patients had a maximum serum lactate of 8.4 [4.3-14] mMol/L and a lowest cardiac index of 1.76 [1.45-2.9] L/min/m2. Nonresponders were connected later to HVHF, displayed progressive tachycardia and decreasing stroke volume. The opposite was true for HVHF-responders who also received targeted-HVHF compounded by aggressive hyperoncotic albumin, sodium bicarbonate and calcium supplementation plus ultrafiltration to avoid fluid overload. All patients survived, but one of the ECMO patients suffered a vascular complication. Conclusion: HVHF may contribute to support severe HCPS patients avoiding the need for ECMO in some of them. Early connection and targeted-HVHF may increase the chance of success.