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To assess the effects of various concentrations of dexmedetomidine on the human blood coagulation profile using rotational thromboelastometry (ROTEM). Venous blood samples were collected from 11 healthy volunteers and divided into four specimen bottles; dexmedetomidine was added to attain final sample concentrations of 0, 0.5, 1.0, and 1.5 ng/mL. ROTEM was performed on each study sample. The concentration of dexmedetomidine increased, and the ROTEM values showed a hypercoagulable state. The change in clotting time (CT) for INTEM was larger in samples with a dexmedetomidine concentration of 1.5 ng/mL (− 34%) than in the 0.5 ng/mL samples (− 16%) (P = 0.010). The change in clot formation time (CFT) for INTEM was greater in 1.5 ng/mL samples (− 16%) than in 0.5 ng/mL samples (− 4%) (P = 0.004). A greater decrease in CT for EXTEM was identified in the 1.0 ng/mL and 1.5 ng/mL samples (− 36% and − 37%, respectively) than in the 0.5 ng/mL samples (− 12%) (P = 0.003 for both categories). The change in CFT for EXTEM was greater in the 1.0 ng/mL and 1.5 ng/mL samples (− 11% and − 13%, respectively) than in the 0.5 ng/mL samples (− 4%) (P = 0.006 and P = 0.001, respectively). A bigger change in maximum clot firmness (MCF) for EXTEM was observed in the 1.5 ng/mL samples (4%) than in the 0.5 ng/mL samples (0%) (P = 0.002). The change in MCF for FIBTEM was greater in the 1.5 ng/mL samples (19%) than in the 0.5 ng/mL samples (5%) (P = 0.001). All coagulation pathways showed a hypercoagulable state as the concentration of dexmedetomidine increased. Nevertheless, most of the values of ROTEM were maintained within the reference ranges. Clinical Trial NCT04269278.