Both metabolic syndrome and sleep disorder are major health problems. Leptin, orexin, ghrelin are implicated in regulation of energy homeostasis and sleep/wakefulness. The levels of these substances exhibit circadian fluctuations, and abnormalities in these rhythms were observed in those disorders. Serum leptin levels were increased during night. Cerebrospinal fluid orexin A levels were increased during active phase. Plasma ghrelin concentrations were increased before meals and during night. High concentrations of leptin during sleep might help keeping sleep by inhibition of feeding behavior and arousal through inhibition of neuropeptide Y and orexin neurons. On the contrary, high concentrations of ghrelin before meal might enhance wakefulness through activation of orexin neurons. These results suggest that the circadian rhythms of these substances are important for maintenance of normal energy homeostasis and sleep/wakefulness.