Extracorporeal membrane oxygenation (ECMO) with a renal replacement therapy such as continuous venovenous hemofiltration (CVVH) provides life-saving temporary heart and lung, and renal support in pediatric and neonatal intensive care units. However, studies have shown that this approach may be hampered due to the potentially inaccurate fluid delivery∕drainage of current intravenous (IV) fluid pumps, creating potential for excessive fluid removal and undesired degrees of dehydration. We present a simple and novel accurate fluid management system capable of working against the high volume flow and pressures typically seen in patients on ECMO. The accuracy of the in-line system implemented at Children’s Healthcare of Atlanta at Egleston was assessed experimentally. The data assisted in the development of a novel automated and accurate fluid management system that functions based on a conservation of volume approach to limit the inaccuracies observed in typical clinical implementations of CVVH. IV pump accuracy measurements demonstrated a standard error in net ultrafiltrate volume removed from the patient of up to over a period of , supporting previous observations of patient’s dehydration during the course of a combined ECMO-CVVH treatment and justifying the need for a new fluid management system. The innovative design of the new device is expected to achieve either a perfect or controlled negative fluid balance between the ultrafiltrate and replacement fluid flow rates. Perfect fluid balance is achieved by imposing an identical displacement on two pistons, one delivering replacement fluid to the circuit and the other draining ultrafiltrate from the hemofilter. Fluid removal is managed via a second syringe-pump system that reduces the net replacement fluid flow rate with respect to the ultrafiltration flow rate. The novel fluid management system described in this paper is expected to provide an effective method to control precisely fluid flow rates in patients on ECMO. Therefore, this device could potentially improve the efficacy of ECMO therapy and constitute a safe and effective way of reducing fluid overload in patients with cardiorespiratory failure.