The effect of the volatile anesthetic desflurane on spinal and cortical somatosensory evoked potentials (SEPs) was examined in 11 Sprague-Dawley male rats. Platinum recording electrodes were placed stereotactically over the left somatosensory cortex and dorsal midline of the T11–12 spinal cord while the right posterior tibial nerve was stimulated at twice motor threshold. The effect of desflurane was examined at various concentrations ranging from 0.7 to 11.4% (2 MAC). Mean arterial blood pressure (MAP) decreased (p = 0.001) progressively with increasing end-tidal desflurane concentrations. Concentrations of 1.4% (1/4 MAC) and 2.8% (1/2 MAC) did not significantly affect the spinal SEP (SSEP) amplitude or the latency. With higher concentrations, there was a progressive decrease in amplitude of the cortical SEPs (CSEPs; p = 0.002) and SSEPs (p = 0.008). However, CSEP and SSEP latencies did not change. At 5.7% (1 MAC), three animals (33%) lost CSEPs while SSEPs remained intact. At 11.4% (2 MAC), the CSEPs were lost in all animals. Only one rat lost the SSEPs at the 2 MAC concentration of desflurane, indicating the resistance of the SSEPs to desflurane anesthesia. We conclude that desflurane anesthesia significantly alters the amplitude of SSEPs and CSEPs without a significant change in the peak latency.