Extracorporeal CO2 removal (ECCO2R) is intended to facilitate lung protective ventilation in patients with hypercarbia. The combination of continuous renal replacement therapy (CRRT) and minimal-flow ECCO2R offers a promising concept for patients in need of both. We hypothecated that this system is able to remove enough CO2 to facilitate lung protective ventilation in mechanically ventilated patients. In 11 ventilated patients with acute renal failure who received either pre- or postdilution CRRT, minimal-flow ECCO2R was added to the circuit. During 6 h of combined therapy, CO2 removal and its effect on facilitation of lung-protective mechanical ventilation were assessed. Ventilatory settings were kept in assisted or pressure-controlled mode allowing spontaneous breathing. With minimal-flow ECCO2R significant decreases in minute ventilation, tidal volume and paCO2 were found after one and three but not after 6 h of therapy. Nevertheless, no significant reduction in applied force was found at any time during combined therapy. CO2 removal was 20.73 ml CO2/min and comparable between pre- and postdilution CRRT. Minimal-flow ECCO2R in combination with CRRT is sufficient to reduce surrogates for lung-protective mechanical ventilation but was not sufficient to significantly reduce force applied to the lung. Causative might be the absolute amount of CO2 removal of only about 10% of resting CO2 production in an adult as we found. The benefit of applying minimal flow ECCO2R in an uncontrolled setting of mechanical ventilation might be limited.