Objective To explore whether the inhaled anesthetic sevoflurane after repeated exposure causes dendritic spine remodeling of neuronal neurons in young mice through the Tau/tubulin tyrosine like ligase 6 (TTLL6)/microtubule dissecting protein (Spastin) signaling pathway. Methods A total of 44 juvenile [postnatal 6 d (P6)] and adult [postnatal 60 d (P60)] mice were selected. According to the random number table method, the mice were divided into four groups (n=11): a juvenile control group (the P6con group), a juvenile anesthesia group (the P6sevo group), an adult control group (the P60con group) and an adult anesthesia group (the P60sevo group). The P6sevo and P60sevo groups were administered with 3% sevoflurane+60% oxygen for 3 d, 2 h/d; while the P6con and P60con groups were given 60% oxygen for 3 d, 2 h/d. On the day after molding, mouse hippocampus tissue was collected to detect the levels of postsynaptic dense protein 95 (PSD95), Tau, TTLL6 and Spastin by Western blot. The expression of Tau, TTLL6 and Spastin, and the co‑location of Tau and TTLL6 were detected by immunofluorescence. Results Compared with the P6con group, the P6sevo group showed decreases in the levels of hippocampal PSD95 (P<0.05), and increases in the levels of Spastin (P<0.05), without statistical difference in Tau and TTLL6 expression (both P>0.05). There was no statistical difference in hippocampal PSD95, Tau, TTLL6 and Spastin levels between the P60con group and the P60sevo group (all P>0.05). The results of immunofluorescence staining showed that Tau and TTLL6 were co‑localized in the P6con group and the P6sevo group, while the co‑localization of Tau and TTLL6 in the hippocampal tissue of the P60con and P60sevo groups was not obvious. Compared with the P6con group, repeated exposure to sevoflurane resulted in remarkable increases in the number of Tau‑, TTLL6‑ and Spastin‑positive cells in the hippocampus of the P6sevo group (all P<0.05). The above changes were not significantly in adult mice (P>0.05). Conclusion Sevoflurane causes dendritic spine remodeling in young rat neurons through the Tau/TTLL6/Spastin signaling pathway.