Hypocretin/orexin neurons are essential to stabilize sleep, but the underlying mechanisms remain elusive. We report that hypocretin neurons of the perifornical hypothalamus are highly active during rapid eye movement sleep and show state-specific correlation with noradrenergic neurons. Deletion of hypocretin gene significantly increased periodic reactivations of locus coeruleus noradrenergic neurons during sleep and dysregulated their activity across transitions, suggesting a role for hypocretin neurons in mediating neuromodulation to stabilize sleep.