Objective To observe the effectiveness and safety of different doses of esketamine combined with propofol for intravenous administration in the child patients undergoing enhanced computed tomography （CT） examination， and to clarify the optimal clinical dose of esketamine in combination with propofol for sedation. Methods This study is a randomized， controlled， double-blind （blinded to subjects and evaluators）， and single-center clinical trial. A total of 120 preschool children undergoing enhanced CT examination were randomly divided into propofol group （P group）， propofol+0.3 mg·kg^-1 esketamine group （P+K3 group）， and propofol+0.5 mg·kg^-1 esketamine group （P+K5 group）， and there were 40 cases in each group. All the children were given 2 mg·kg^-1 propofol， and additional propofol was administered in increments of 1 mg·kg^-1 until the sedation criteria for entering the CT room were met ［Modified Observer’s Assessment of Alertness/Sedation （MOAA/S） score ≤3］. The vital signs of the children were observed and recorded at four time points： before sedation （T₀）， when sedation was satisfactory （T₁）， during contrast agent injection （T₂）， and upon awakening （T₃）. The examination time， time to satisfactory sedation （from the start of sedation to MOAA/S score≤3）， and awakening time （from the end of the examination to MOAA/S score>4） of the children in various groups were recorded. The total dose of propofol and the proportion of cases requiring additional propofol were compared among various groups. Adverse reactions during induction， examination， and after awakening were also compared among various groups. Results There were no significant differences in general conditions of the children in three groups （P>0.05）. Hemodynamic parameters： at T₂， compared with P group， the SpO₂ levels of the children in P+K3 group and P+K5 group were increased （P<0.05）； at T₁， compared with P group， the SBP levels of the children in P+K3 group and P+K5 group were increased （P<0.05）. There were no significant differences in examination time of the children in three groups （P>0.05）. Compared with P group and P+K3 group， the time to satisfactory sedation of the children in P+K5 group was shorter （P<0.05）. Compared with P group， the awakening time of the children in P+K3 group and P+K5 group was shorter （P<0.05）. Compared with P group and P+K3 group， the total dose of propofol of the children in P+K5 group was decreased （P<0.05）， and the proportion of cases requiring additional propofol was lower （P<0.05）. Adverse reaction indicators： compared with P group， the incidence of respiratory depression of the children in P+K3 group and P+K5 group was lower （P<0.05）， and the incidence of nausea and vomiting was lower （P<0.05）. Compared with P group and P+K3 group， the incidence of movement during the examination of the children in P+K5 group was lower （P<0.05）， and the incidence of dizziness was higher （P<0.05）. There were no significant differences in the incidence of increased airway secretions of the children in three groups （P>0.05）. Conclusion The use of 0.5 mg·kg^-1 esketamine combined with 2 mg·kg^-1 propofol for intravenous administration in the child patients for enhanced CT examination sedation can improve the efficiency of such examinations and offers high safety and effectiveness.