Sevoflurane is one of the most commonly used volatile anaesthetics for children, but the safety of prolonged or repeated clinical use of sevoflurane in infants or children is controversial. Here, we investigated the effects of sevoflurane on rats in early life and the time scale of those effects. Our behavioral results indicated that repeated short-term exposure of new-born rats to sevoflurane caused learning and memory impairment, while a single exposure of rats to sevoflurane was relatively safe. Further mechanistic investigation revealed that repeated sevoflurane exposure impaired long-term potentiation (LTP), downregulated the expression of certain synaptogenesis-related proteins (GluR1, PSD95) and upregulated proteins related to endoplasmic reticulum (ER) stress in the hippocampus. An ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), reversed the changes in the levels of synaptic plasticity proteins. Our results provide new evidence for the clinical concerns regarding repeated sevoflurane anesthesia.