Background <p>The available data on the effect of dexmedetomidine premedication on anesthesia depth in children during general anesthesia are limited. This study was designed to determine the effect of preoperative dexmedetomidine administration on the bispectral index (BIS) and sevoflurane requirements in children during sevoflurane anesthesia.</p> Methods <p>120 children aged 5 to 12 years undergoing concealed penis repair or hypospadias plastic surgery were randomized to receive preoperative administration of 0.25&#xa0;µg kg^− 1 dexmedetomidine, 0.5&#xa0;µg kg^− 1 dexmedetomidine, 0.75&#xa0;µg kg^− 1 dexmedetomidine, or the same volume of placebo. The primary outcome was the change in the BIS value from before dexmedetomidine administration to 60&#xa0;min after surgical incision. The secondary outcomes included the end-tidal sevoflurane concentration (ETsevo), hemodynamic data, anesthesia recovery data and intraoperative awareness.</p> Results <p>Compared with those in Group C, the BIS values of children in Group D2 and Group D3 were significantly lower during sevoflurane induction and early maintenance (<i>P</i> &lt; 0.017). Moreover, children in Group D2 and Group D3 had a lower ETsevo (<i>P</i> &lt; 0.001) during sevoflurane maintenance than did those in Group C (<i>P</i> &lt; 0.017). There were statistically significant differences in heart rate(<i>P</i> &lt; 0.0001) and mean arterial pressure(<i>P</i> &lt; 0.001) between the groups, but the incidence of bradycardia or hypotension was similar between the groups (<i>p</i> = 0.779 and <i>p</i> = 0.901).</p> Conclusions <p>Children who received 0.5&#xa0;µg kg^− 1 or 0.75&#xa0;µg kg^− 1 dexmedetomidine preoperatively were more likely to achieve the target depth of anesthesia (BIS less than 60) during anesthesia induction and had lower BIS values during the early stage of anesthesia maintenance.</p> Trail registration <p>The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR1900026872. Date of registration: 10/24/2019.</p>