In the mammalian brain, sleep and wakefulness are associated with widespread changes in gene expression. The extent to which the molecular correlates of vigilance state are conserved across phylogeny, however, is only beginning to be explored. The goal of this study was to determine whether sleep and wakefulness affect gene expression in the avian brain. To achieve this end we performed an extensive microarray analysis of gene expression during sleep, wakefulness, and short-term sleep deprivation in the telencephalon of the white-crowned sparrow (Zonotrichia leucophrys gambelii). We found that, as in the rodent cerebral cortex, behavioral state, independent of time of day, has widespread effects on avian brain gene expression, affecting the transcript levels of 255 genes (1.4% of all tested transcripts). Wakefulness-related transcripts (n = 114) code for proteins involved in energy metabolism and oxidative phosphorylation, immediate early genes and transcription factors associated with activity-dependent neural plasticity, as well as heat-shock proteins and molecular chaperones associated with the unfolded protein response. Sleep-related transcripts (n = 141) code for proteins involved in membrane trafficking, lipid/cholesterol synthesis, translational regulation, cellular adhesion, and cytoskeletal organization. Remarkably, despite the considerable differences in morphology and cytology between the mammalian neocortex and the avian telencephalon, the functional categories of transcripts identified in this study exhibit a significant degree of overlap with those identified in the rodent cortex.