Purpose: The goal of this study was to explore possible microcirculatory alterations by changing sedative infusion from propofol to midazolam in patients with septic shock. Materials and Methods: Patients (n = 16) were sedated with propofol during the first 24 hours after intubation, then with midazolam, following a predefined algorithm. Systemic hemodynamics, perfusion parameters, and microcirculation were assessed at 2 time points: just before stopping propofol and 30minutes after the start of midazolam infusion. Sublingual microcirculation was evaluated by sidestream dark-field imaging. Results: The microvascular flow index and the proportion of perfused small vessels were greater when patients were on midazolam than when on propofol infusion (2.8 [2.4-2.9] vs 2.3 [1.9-2.6] and 96.4%[93.7%-97.6%] vs 92.7% [88.3%-94.7%], respectively; Pb.005), and the flow heterogeneity index was greater with propofol than with midazolam use (0.49 [0.2-0.8] vs 0.19 [0.1-0.4],Pb.05). There were nosignificant changes in systemic hemodynamics and perfusion parameters either during propofol use orduring midazolam infusions. Data are presented as median (25th-75th percentiles). Conclusions: In this study, sublingual microcirculatory perfusion improved when the infusion was changed from propofol to midazolam in patients with septic shock. This observation could not be explained by changes in systemic hemodynamics.