Brain imaging studies demonstrate that sleep deprivation reduces glucose metabolism and blood flow in the prefrontal cortex, and such reductions are associated with impairments in cognitive functioning. Although some of the greatest metabolic declines occur within the orbitofrontal cortex, little is known about the effects of sleep loss on the types of processes mediated by this region, including emotion, motivation, feeding, and olfaction. The present study tested odor identification accuracy when individuals were well rested and again following 24 h of wakefulness. Relative to rested baseline performance, sleep-deprived individuals demonstrated a significant decline in the ability to identify specific odors on the Smell Identification Test. This decrement in olfactory functioning occurred concomitantly with slowed psychomotor speed and increased ratings of self-reported sleepiness. Performance on a task that required complex mental set shifting did not change significantly following sleep deprivation, suggesting that the decrements in odor identification could not be attributed to task difficulty. Finally, while there was no relationship between subjective sleepiness and odor identification at rested baseline, greater subjective sleepiness was associated with better odor identification ability following 24 h of sleep loss. Possible implications of these findings are discussed.