PURPOSE: To investigate whether COVID-19-ARDS differs from all-cause ARDS. METHODS: Thirty-two consecutive, mechanically ventilated COVID-19-ARDS patients were compared to two historical ARDS sub-populations 1:1 matched for PaO(2)/FiO(2) or for compliance of the respiratory system. Gas exchange, hemodynamics and respiratory mechanics were recorded at 5 and 15 cmH(2)O PEEP. CT scan variables were measured at 5 cmH(2)O PEEP. RESULTS: Anthropometric characteristics were similar in COVID-19-ARDS, PaO(2)/FiO(2)-matched-ARDS and Compliance-matched-ARDS. The PaO(2)/FiO(2)-matched-ARDS and COVID-19-ARDS populations (both with PaO(2)/FiO(2) 106 ± 59 mmHg) had different respiratory system compliances (Crs) (39 ± 11 vs 49.9 ± 15.4 ml/cmH(2)O, p = 0.03). The Compliance-matched-ARDS and COVID-19-ARDS had similar Crs (50.1 ± 15.7 and 49.9 ± 15.4 ml/cmH(2)O, respectively) but significantly lower PaO(2)/FiO(2) for the same Crs (160 ± 62 vs 106.5 ± 59.6 mmHg, p < 0.001). The three populations had similar lung weights but COVID-19-ARDS had significantly higher lung gas volume (PaO(2)/FiO(2)-matched-ARDS 930 ± 644 ml, COVID-19-ARDS 1670 ± 791 ml and Compliance-matched-ARDS 1301 ± 627 ml, p < 0.05). The venous admixture was significantly related to the non-aerated tissue in PaO(2)/FiO(2)-matched-ARDS and Compliance-matched-ARDS (p < 0.001) but unrelated in COVID-19-ARDS (p = 0.75), suggesting that hypoxemia was not only due to the extent of non-aerated tissue. Increasing PEEP from 5 to 15 cmH(2)O improved oxygenation in all groups. However, while lung mechanics and dead space improved in PaO(2)/FiO(2)-matched-ARDS, suggesting recruitment as primary mechanism, they remained unmodified or worsened in COVID-19-ARDS and Compliance-matched-ARDS, suggesting lower recruitment potential and/or blood flow redistribution. CONCLUSIONS: COVID-19-ARDS is a subset of ARDS characterized overall by higher compliance and lung gas volume for a given PaO(2)/FiO(2), at least when considered within the time frame of our study.