Sepsis is a major cause of death and the most common cause of death among critically ill, non-ICU patients. Dexmedetomidine (DEX), an adrenergic receptor agonist, presents sympatholytic action in certain parts of the brain with anxiolytic, sedative, and pain killing effects. Additionally, through the activation of nicotinic acetylcholine receptor receptors, DEX reduces cytokine transcription and inhibits inflammation, rendering it beneficial during septic conditions. Moreover, there is a lot of interest in designing experimental sepsis models, where the administration of DEX is evaluated for its impact on multiple systems. This review focuses on experimental studies published between 1999 to March 2019 that were using DEX administration in sepsis in vivo models. From these, 36 articles were selected and summarized. Overall results show evidence that DEX may decrease mortality and inhibit inflammation, as it enhances the activity of the immune system while reducing its systemic reaction and lowering cytokine concentrations. Moreover DEX succeeds to alleviate heart injury during sepsis, acting beneficially for microcirculation and shows a neuroprotective role by inhibiting apoptotic pathways. In addition, DEX appears to have a protective role for liver and spleen as well as a beneficial role for the function of lungs and kidneys as it reduces sepsis-induced injuries and apoptosis in intra-abdominal experimental sepsis models.