Objective: To compare the effects of a propofol-based versus dexmedetomidine-basedsedation regimen for mechanically ventilated patients with sepsis.Methods: Single-center, randomized, open-label interventional study of critically ill patientsadmitted to the intensive care unit with sepsis and respiratory failure requiring mechanicalventilation. Patients were sedated with either propofol or dexmedetomidine.Results: Thirty-six patients with sepsis and respiratory failure requiring mechanical ventilationwere randomly assigned to receive sedation with either dexmedetomidine or propofol. Fentanylwas used for analgesia in both groups. The primary end point was duration of mechanicalventilation, and secondary end points included 28-day mortality, the duration of ICU stay, and theduration of vasopressor support. There was a non-statistically significant trend toward decreasedduration of mechanical ventilation in the dexmedetomidine group (p = 0.107), and multivariableanalysis demonstrated a small to moderate effect size in the sample. There were no significantdifferences in 28-day mortality, duration of ICU stay, or duration of vasopressor requirement. Nopatients required discontinuation of study drug due to adverse effects.Conclusions: Although underpowered for statistical significance, there was a trend towarddecreased duration of mechanical ventilation with dexmedetomidine. More studies with higherpatient enrollment are needed to determine whether the duration of mechanical ventilation inpatients with sepsis who receive sedation with dexmedetomidine is reduced when comparedto propofol.