The effects of sleep deprivation on behavior and cognition have generally been understood in terms of a homeostatic process that increases the drive for sleep with extended wakefulness, a process whose neurochemical origins have recently begun to be elucidated. As decrements in vigilance and attention are among the first signs of sleep loss and sleepiness, it has been hypothesized that common neural systems are involved in the processes of the sleep drive and sustained attention. For example, the activity of the basal forebrain cholinergic system has been proposed to promote cortical arousal and wakefulness as well as attention. Furthermore, we and others have hypothesized that an inhibition of this cortically projecting cholinergic system mediates the sleepiness associated with prolonged wakefulness. We only know of one study that has used an attentional measure in a behavioral assessment of sleep-deprived animals. Hence, the goal of the present study was to develop a rodent model of the attentional dysfunction caused by sleep loss that could be used to elucidate the effects of sleep drive on neurobiological processes of attention. The attentional performance of rats was assessed after 4, 7, and 10 h of total sleep deprivation (SD) on a 5CSRTT, where rats detect and respond to brief visual stimuli. SD produced a monotonic increase in response latencies across the three deprivations. SD also led to increased omission errors, but the overall number of perseverative and premature responses was unchanged. The effects of sleep deprivation on rats are compatible with a range of human findings on the effects of sleepiness on selective attention, psychomotor vigilance, and behavioral control. Rats also exhibited differential susceptibility to the effects of sleep deprivation, consistent with ‘trait-like’ susceptibility that has been found in humans. These findings indicate the feasibility of using the 5CSRTT as an animal model for investigating the direct links between homeostatic sleep mechanisms and resulting attentional impairments within a single animal subject.