Background: Dexmedetomidine (Dex), as a new and highly selective alpha 2 adrenergic receptor agonist, has been widely used in mechanically ventilated patients. In the present study, we used meta-analysis to study the effect of Dex on the prognosis of mechanically ventilated patients with sepsis. Methods: We searched PubMed, Cochrane clinical trial, EMBASE, Web of Science, and Chinese biomedical literature database to analyze relevant literature published from January 2000 to January 2021. We conducted the quality evaluation and data extraction for studies that met the inclusion criteria. RevMan 5.3 software was used to perform a meta-analysis of the 28- day mortality, hospital mortality, the length of ICU stay, and other adverse indicators. Results: Ten randomized controlled trials (RCTs) that met the inclusion criteria were finally included, including 9 RCTs in English and one in Chinese, with a total of 892 patients. Our meta-analysis results found that in mechanically ventilated patients with sepsis, Dex could significantly reduce the length of ICU stay ( P=0.02), but did not reduce the patients' 28-day mortality (P= 0.06), hospital mortality (P=0.17) and ventilator-free days ( P=0.33). Furthermore, our meta-analysis results also found that Dex had no significant effect on the respiratory rate (P=0.53), heart rate (P=0.02), mean arterial pressure (P=0.63), the level of creatinine (P=0.82) and continuous renal replacement therapy (P=0.39) in mechanically ventilated patients with sepsis. Conclusion: In mechanically ventilated patients with sepsis, Dex can reduce the length of ICU stay, but which cannot reduce the 28-day mortality, hospital mortality, and ventilator-free days.