Anesthesia-induced neurotoxicity in immature animals has raised concerns about similar effects occurring in young children. Our study investigated two commonly used anesthetics-sevoflurane and propofol-for neurotoxicity in young children. Forty-seven children (aged 12-36 months) undergoing hypospadias repair surgery were randomized to receive sevoflurane (SG, n = 24) or propofol (PG, n = 23) general anesthesia. Venous blood was collected at three different times-immediately after induction, 2 h, and 3 days after surgery. The cellular portion was assessed for antioxidant defense and DNA damage, using enzyme assay kits and qRT-PCR, respectively, while serum was used to treat cultured neural stem cells (NSCs). MTT assay and TUNEL staining were performed, and the mRNA levels of antioxidant enzymes and apoptosis indicators were evaluated by qRT-PCR. Antioxidant defense and apoptosis status in the SG group were significantly higher than in the PG group at 2 h after surgery. Additionally, exposure of NSCs to postoperative serum of the SG group resulted in decreased cell density and viability, increased TUNEL-positive cells, elevated mRNA levels of antioxidant enzymes, and cleaved caspase-3 expression. Our data shows for the first time that in young children, administration of sevoflurane, but not propofol, leads to temporally increased antioxidant defense and apoptosis status as well as damage of NSCs.