Background: A recent study discovered that exposure to the anesthetic gas sevoflurane in the early years of life can impact cognitive function. Objectives: This study aims to investigate the effects of prolonged and repeated exposure to sevoflurane during the weaning period and whether the administration of propolis, a well-known herbal substance with anti-inflammatory properties, has a beneficial effect on inflammation and synaptic markers in the prefrontal cortex area, as well as its effect on spatial working memory function. Methods: We utilized Sprague Dawley rats aged 21 days (P21), divided into three groups: Control, sevoflurane, and sevoflurane with propolis. The exposure to sevoflurane (3%) was conducted three times for 2 hours each at P21, P23, and P25. Propolis treatments were administered orally for four weeks, starting from the first day of exposure to sevoflurane. Analyses of IL-6, TNF-alpha, and IL-10 levels were performed using ELISA at P25 and P51, while spatial working memory was measured using the spontaneous Y-maze. Results: Exposure to sevoflurane during the weaning period had no effect on IL-6, TNF-alpha, IL-10, and PSD95 levels in the prefrontal cortex, nor on working memory function. Similarly, the administration of propolis did not have any beneficial effect on these parameters. Conclusions: Prolonged and repeated exposure to sevoflurane during the weaning period did not induce neuroinflammation conditions that would affect synaptic markers and working memory function. Further studies are required to identify a dose of sevoflurane that causes detrimental effects on memory function and to explore the beneficial effects of propolis on this condition.