Working memory is very sensitive to acute sleep deprivation, and many studies focus on the brain areas or network activities of working memory after sleep deprivation. However, little is known about event-related potential (ERP)-related changes in working memory after sleep loss. The purpose of this research was to explore the effects of 36 h of total sleep deprivation (TSD) on working memory through ERPs. Sixteen healthy college students performed working memory tasks while rested and after 36 h of TSD, and electroencephalography (EEG) data were simultaneously recorded while the subjects completed working memory tasks that included different types of stimulus materials. ERP data were statistically analyzed using repeated measurements analysis of variance to observe the changes in the working memory-related N2-P3 components. Compared with baseline before TSD, the amplitude of N2-P3 components related to working memory decreased, and the latency was prolonged after TSD. However, the increased amplitude of the P2 wave and the prolonged latency were found after 36 h of TSD. Thus, TSD can impair working memory capacity, which is characterized by lower amplitude and prolonged latency.