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Background: PEEP selection in severe COVID-19 patients under extracorporeal membrane oxygenation (ECMO) is challenging as no study has assessed the alveolar recruitability in this setting. The aim of the study was to compare lung recruitability and the impact of PEEP on lung aeration in moderate and severe ARDS patients with or without ECMO, using computed tomography (CT)., Methods: We conducted a two-center prospective observational case-control study in adult COVID-19-related patients who had an indication for CT within 72 h of ARDS onset in non-ECMO patients or within 72  h after ECMO onset. Ninety-nine patients were included, of whom 24 had severe ARDS under ECMO, 59 severe ARDS without ECMO and 16 moderate ARDS., Results: Non-inflated lung at PEEP 5 cmH 2 O was significantly greater in ECMO than in non-ECMO patients. Recruitment induced by increasing PEEP from 5 to 15 cmH 2 O was not significantly different between ECMO and non-ECMO patients, while PEEP-induced hyperinflation was significantly lower in the ECMO group and virtually nonexistent. The median [IQR] fraction of recruitable lung mass between PEEP 5 and 15 cmH 2 O was 6 [4-10]%. Total superimposed pressure at PEEP 5 cmH 2 O was significantly higher in ECMO patients and amounted to 12 [11-13] cmH 2 O. The hyperinflation-to-recruitment ratio (i.e., a trade-off index of the adverse effects and benefits of PEEP) was significantly lower in ECMO patients and was lower than one in 23 (96%) ECMO patients, 41 (69%) severe non-ECMO patients and 8 (50%) moderate ARDS patients. Compliance of the aerated lung at PEEP 5 cmH 2 O corrected for PEEP-induced recruitment (C BABY LUNG ) was significantly lower in ECMO patients than in non-ECMO patients and was linearly related to the logarithm of the hyperinflation-to-recruitment ratio., Conclusions: Lung recruitability of COVID-19 pneumonia is not significantly different between ECMO and non-ECMO patients, with substantial interindividual variations. The balance between hyperinflation and recruitment induced by PEEP increase from 5 to 15 cmH 2 O appears favorable in virtually all ECMO patients, while this PEEP level is required to counteract compressive forces leading to lung collapse. C BABY LUNG is significantly lower in ECMO patients, independently of lung recruitability., (© 2022. The Author(s).)