Insulin-like growth factor 1 (IGF-1) is a neuroprotective hormone and a decrease in levels of circulating IGF-1 contributes toward cognitive decline. The aim of this study was to investigate the effect of sevoflurane on the level of circulating IGF-1 and cognitive function in aged mice and the role of circulating IGF-1 in the cognitive dysfunction induced by sevoflurane. Aged mice were exposed to 1 or 2 minimal alveolar concentrations of sevoflurane for 4 or 8 h. Before and after the exposure, blood was collected from the tail vein and serum IGF-1 was measured by an enzyme-linked immunosorbent assay. After exposure, spatial learning and memory were tested in the Morris water maze. An intraperitoneal injection of IGF-1 was used to study the role of IGF-1 in the cognitive impairment induced by sevoflurane. Sevoflurane dose dependently decreased the serum IGF-1 concentration, and resulted in aged mice taking significantly longer and traveling significantly further to find the platform. Sevoflurane significantly decreased the times crossing the platform and %time spent in target quadrant relative to the control group. IGF-1 attenuated this effect, but could not completely reverse it. We conclude that downregulation of circulating IGF-1 contributes toward the cognitive impairment induced by sevoflurane.