Objective To explore the inhibitory effect of coenzyme Q10 (CoQ10) on ferroptosis in hippocampal tissue induced by repeated exposure to sevoflurane in rats at the peak of development via the nicotinamide adenine dinucleotide phosphate (NADPH)/glutathione peroxidase 4 (GPX4) signaling pathway and its effect on neurological function. Methods A total of 141 Sprague‑Dawley rats, at postnatal day 7 (P7), were exposed to 2% sevoflurane for 4 h/day over three days, in order to establish an animal model for repeated sevoflurane exposure. According to the random number table method, 138 rats were divided into six groups (n=23): a blank control group (group A, a mixture of 30% O2 and 70% N2 gas at 4 h/day for 3 days), a repeated anesthesia group (group B, 2% sevoflurane at 4 h/day for 3 days), a blank control+CoQ10 mimetic pretreatment group (group C, the mixture of 30% O2 and 70% N2 gas at 4 h/day+CoQ10 mimetic pretreatment for 3 days), a repeated anesthesia+CoQ10 mimetic pretreatment group (group D, 2% sevoflurane 4 h/day+CoQ10 mimetic pretreatment for 3 days), a blank control+CoQ10 inhibitor pretreatment group (group E, the mixture of 30% O2 and 70% N2 gas at 4 h/day+CoQ10 inhibitor pretreatment for 3 days), and a repeat anesthesia+CoQ10 inhibitor pretreatment group (group F, 2% sevoflurane 4 h/day+CoQ10 inhibitor pretreatment for 3 days). The remaining three mice were classified as a single anesthesia group (group B‑1, 2% sevoflurane for 4 h, for blood gas testing alone). After the end of experiments in each group, blood samples were first drawn from the left ventricle of the three mice for blood gas analysis, so as to confirm the safety of the experimental animal model. Then, six rats were chosen from each group (except group B-1) and the head and brain were collected to isolate hippocampal tissues. The contents of ferrous ion (Fe2+) and glutathione (GSH) were detected by colorimetry with kits, and the amount of 4‑hydroxynonenal (4‑HNE) was measured by enzyme‑linked immunosorbent assay (ELISA). Furthermore, another six rats were chosen from each group for detecting the levels of GPX4 and NADPH protein by Western blot. Additionally, eight rats were selected from each group for long‑term feeding. The Morris water maze test was conducted when the rats grew to 4 and 20 weeks. The learning and memory abilities of these rats were assessed through their swimming distance to reach the platform in the localization navigation experiment, the number of times they crossed the position of the original platform in the spatial exploration experiment, the time to swim in the quadrant where the original platform was located, and the time required to cross the position of the original platform for the first time. Results Rats in each group had total carbon dioxide (TCO2), pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), hydrocarbonate (HCO−3), and pulse oxygen saturation (SpO2) within a normal range, without statistical differences (all P>0.05). Compared with group A, the hippocampal tissues in group B showed increases in Fe2+ and 4‑HNE contents (all P<0.05), decreases in GSH content, and reduced levels of GPX4 and NADPH protein (all P<0.05), as well as an decreased number of times that rats crossed the position of the original platform (P<0.05), shortened time to swim in the quadrant where the original platform was located (P<0.05), and extended time required to cross the position of the original platform for the first time (P<0.05). Compared to group B, the hippocampal tissues in group D presented decreases in Fe2+ and 4‑HNE contents (all P<0.05), increases in GSH content (P<0.05), up‑regulated levels of GPX4 and NADPH protein (all P<0.05), as well as an increased number of times that rats crossed the position of the original platform (P<0.05), extended time to swim in the quadrant where the platform was located (P<0.05), and shortened time required to cross the position of the original platform for the first time (P<0.05). In contrast, group F showed increases in Fe2+ and 4‑HNE contents (all P<0.05), decreases in GSH content (P<0.05), reduced levels of GPX4 and NADPH protein (all P<0.05), as well as a decreased number of times the rats crossed the location of the original platform (P<0.05), and shortened time to swim in the quadrant where the platform was located (P<0.05), and extended time required to cross the position of the original platform for the first time (P<0.05). Conclusions Repeated exposure to sevoflurane in P7 rats triggers ferroptosis and decline of learning and memory ability after growth. CoQ10 inhibits ferroptosis caused by repeated exposure to sevoflurane via the NADPH/GPX4 pathway, with neuroprotective effect.