The lateral hypothalamus (LH) is a relatively large hypothalamic structure containing several neurochemically different, but spatially intermingled, neuronal populations. While the role of these neurons in the homeostatic regulation of diverse physiological and behavioral functions such as sleep/wake cycle has been studied extensively, the impact of sleep history on the electrophysiology of the LH and whether this effect is homogenous across LH is unknown. By combining multiunit activity (MUA) recordings in different regions of LH with electroencephalogram recordings in freely moving rats, we unravelled a heterogeneity of neural-activity patterns within different subregions of LH. This heterogeneity was evident in both the circadian and the vigilance state-dependent modulation of MUA. Interestingly, and consistent with this heterogeneity under baseline conditions, the magnitude of MUA suppression following 6 hr of sleep deprivation (SD) was also different within different locations of LH. Unlike the cortex and in contrast to the predictions of the synaptic homeostatic hypothesis, no correlation was found between the magnitude of activity increase during SD and the percentage of suppression of MUA during recovery sleep. These data provide in vivo evidence of a functional heterogeneity in the circadian and homeostatic modulation of neuronal activity in LH.