Objective: Anxiety may have deleterious effects by increasing oxygen consumption (VO2) and energy expenditure (EE) in mechanically ventilated patients. The effects of dexmedetomidine, a selective alpha-2 agonist sedative, have not been studied in critically ill patients in this respect. In this study, the effects of dexmedetomidine on VO 2 and EE in mechanically ventilated critically ill patients were investigated by indirect calorimetry. Materials and Methods: All patients served as their own control. Before commencing dexmedetomidine infusion, baseline values of all parameters were recorded. Then, following a bolus dexmedetomidine dose of 1 µg/kg, infusion started at a dose of 0.2-0.7 µg/kg/h. Sedation was maintained for two hours with dexmedetomidine, which was titrated to provide moderate sedation according to bispectral index (BIS) score. BIS score was aimed to be kept between 60-70 throughout the study. We measured VO 2 , carbon dioxide production (VCO 2) and EE by indirect calorimetry method for two hours during dexmedetomidine infusion. The study was completed after dexmedetomidine infusion was stopped and the measurements were repeated at the first, second, and third hours. Results: Fifteen patients participated in the study. The mean age was 48±16 years and the mean APACHE 2 score was 14.8±6.2. During dexmedetomidine infusion, VO 2 , EE and VCO 2 decreased significantly compared to baseline (p<0.05). After the discontinuation of dexmedetomidine, all variables approached to their baseline values. Conclusion: We concluded that dexmedetomidine attenuated metabolic stress response in critically ill patients and cessation of sedation was followed by increases in VO 2 and EE.