Background: Inappropriate use of intravenous and inhaled anesthetics may be dangerous in infants undergoing facial cleft surgeries. This study primarily aimed to compare the effect of infraorbital nerve block on sevoflurane requirement in infants undergoing cheiloplasty. Intraoperative opioid consumption, hemodynamics, blood glucose levels, extubation time, and delirium were also compared. Methods: This prospective, randomized, double-blinded study was conducted in 34 infants undergoing cheiloplasty under general anesthesia. After induction, group A received bilateral infraorbital nerve block with 0.5 mL of 0.5% bupivacaine and group B 0.5 mL saline. An increase in heart rate or blood pressure > 20% was managed by increasing sevoflurane by 2–2.5%, followed by fentanyl 0.5 µg/kg bolus. The chi-square test and independent-sample t-test were used where applicable. Results: Demographics, duration of surgery, and intravenous fluids used were comparable between the groups.Compared to group A, patients in group B had significantly higher consumption of fentanyl (14.2 ± 4.4 µg vs. 22.1 ± 6.2 µg) and sevoflurane (14.2 ± 4.8 mL vs. 26.8 ± 15.6 mL). Intraoperative hemodynamic parameters were significantly lower in group A, the number of times increases in hemodynamic parameters occurred, and fentanyl supplemental bolus was required remained significantly lower in group A than in group B. Intraoperative glycemic levels remained higher in group B, and the extubation time was significantly shorter in group A than in group B (4.40 ± 1.60 min vs. 9.2 ± 2.18 min). Group A had a lesser occurrence of postoperative delirium. Conclusion Supplemental infraorbital block in infants undergoing cheiloplasty under general anesthesia resulted in significantly decreased anesthetic requirements and optimal hemodynamic and glycemic levels with faster extubation and lesser delirium.