Sleep deprivation has widespread health effects, including increased risk of hypertension, diabetes, obesity, heart attack, and stroke. In addition, it leads to car accidents and medical errors. During sleep deprivation, homeostatic and circadian processes interact to build up sleep pressure, which results in slow behavioral performance (cognitive lapses). Here we used intracranial electrodes to record single-neuron activities and LFPs in human neurosurgical patients performing a face/nonface categorization psychomotor vigilance task (PVT) over multiple experimental sessions, including after full-night sleep deprivation. We find that, just before cognitive lapses, the selective spiking responses of individual MTL neurons are attenuated, delayed, and lengthened. These ‘neuronal lapses’ are evident on a trial-by-trial basis when comparing the slowest behavioral PVT reaction times to the fastest. In addition, during these lapses, LFPs exhibit a relative local increase in ‘sleep-like’ slow/theta activity that invades the activity of the awake brain. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already present in the MTL.