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Abstract Background The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation. Methods Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint. Results Sixteen patients were enrolled and were sedated for 126 h(61–228) in the propofol group and 207 h(171–216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8–21.6) in the propofol group and 20.4cmH2O/l/s(18.6–26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176–290) in the propofol group and 73 ml(35–126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1–3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups. Conclusions In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.