Extracorporeal CO₂ removal (ECCO2R) is a therapeutic approach that allows protective ventilation in acute respiratory failure by preventing hypercapnia and subsequent acidosis. The main indications for ECCO2R in acute respiratory failure are COPD (chronic obstructive pulmonary disease) exacerbation, acute respiratory distress syndrome (ARDS) and other situations of asthmatics status. However, CO₂ removal procedure is not extended to those ARDS patients presenting an air leak. Here, we report three cases of air leaks in patients with an ARDS that were successfully treated using a new ECCO2R device. Case 1 is a polytrauma patient that developed pneumothorax during the hospital stay, case 2 is a patient with a post-surgical bronchial fistula after an Ivor–Lewis esophagectomy, and case 3 is a COVID-19 patient who developed a spontaneous pneumothorax after being hospitalized for a prolonged time. ECCO2R allowed for protective ventilation mitigating VILI (ventilation-induced lung injury) and significantly improved hypercapnia and respiratory acidemia, allowing time for the native lung to heal. Although further investigation is needed, our observations seem to suggest that CO₂ removal can be a safe and effective procedure in patients connected to mechanical ventilation with ARDS-associated air leaks.