Technical Abstract: Behavioral and physiological rhythms can be entrained by daily restricted feeding (RF), indicating the existence of a food-entrainable oscillator (FEO). One manifestation of the presence of FEO is anticipatory activity to regularly scheduled feeding. In the present study, we tested if intact ghrelin signaling is required for FEO function by studying food anticipatory activity (FAA) in preproghrelin knockout (KO) and wild-type (WT) mice. Sleep-wake activity, locomotor activity, body temperature, food intake, and body weight were measured for 12 days in mice on a RF paradigm with food available only for 4 h daily during the light phase. On RF days 1–3, increases in arousal occurred. This response was significantly attenuated in preproghrelin KO mice. There were progressive changes in sleep architecture and body temperature during the subsequent nine RF days. Sleep increased at night and decreased during the light periods while the total daily amount of sleep remained at baseline levels in both KO and WT mice. Body temperature fell during the dark but was elevated during and after feeding in the light. In the premeal hours, anticipatory increases in body temperature, locomotor activity, and wakefulness were present from RF day 6 in both groups. Results indicate that the preproghrelin gene is not required for the manifestation of FAA, but suggest a role for ghrelinergic mechanisms in food deprivation-induced arousal in mice.