Objective To discuss the effectiveness and side effects of dexmedetomidine (Dex) combined with ketamine for drug‑induced sleep endoscopy (DISE) in children with obstructive sleep apnea syndrome (OSAS). Methods According to the random number table method, 70 OSAS children, aged 3 to 12 years, American Society of Anesthesiologists (ASA) ⅠorⅡ, both boys and girls, were divided into two groups (n=35): group A and group B. All the children were intravenously infused with a loading dose of Dex (2 μg/kg) over 10 min followed by intravenous infusion at 1 µg·kg−1·h−1 for anesthesia maintenance. For group A, 1 mg/kg ketamine was added at the beginning of Dex injection. For group B, 1 mg/kg ketamine was added when Dex was intravenously injected for 5 min. Examination started when Ramsay score>5. The first‑attempt success rate was recorded. The vital signs were recorded before induction (T0), when Dex infusion was performed for 5 min (T1) and 10 min (T2) and during examination (T3). The addition of ketamine due to body movement and adverse reactions were recorded. Results Group B presented a higher first‑attempt success rate than group A (P<0.05). Group B produced decreases in pulse oxygen saturation (SpO2) at T2, decreases in heart rate, diastolic blood pressure (DBP), and systolic blood pressure (SBP) at T1, compared with group A (P<0.05). Patients in group A produced decreases in SpO2 and heart rate at T1, T2 and T3, compared with those at T0 (P<0.05); increases in SBP and DBP at T1, T2 and T3, compared with those at T0 (P<0.05); decreases in heart rate at T2 and T3, compared with those at T1 (P<0.05); and decreases in SpO2 at T3, compared with those at T2 (P<0.05). Patients in group B produced decreases in SpO2 and heart rate at T1, T2 and T3, compared with those at T0 (P<0.05); decreases in SBP at T1, compared with those at T0 (P<0.05); increases in SBP at T2, compared with those at T0 (P<0.05); increases in DBP at T2 and T3, compared with those at T0 (P<0.05); decreases in SpO2 at T2 and T3, compared with those at T1 (P<0.05); increases in heart rate and SBP at T2 and T3, compared with those at T1 (P<0.05); increases in DBP at T2, compared with those at T1 (P<0.05); and decreases in DBP at T3, compared with those at T2 (P<0.05). There was no statistical difference in adverse reaction between the two groups (P<0.05). For group B, one patient manifested bradycardia which then improved after intravenous injection of atropine, and another patient manifested secondary atrioventricular block at 3∶2 and 4∶3 at T1 which then disappeared after intravenous injection of ketamine. Conclusions Compared with sequential administration, the simultaneous injection of Dex and ketamine produces less effects on hypoxia and hemodynamics in OSAS children, without severe bradycardia and hypotension. It is a proper anesthesia scheme for DISE in OSAS children.