Orexin binds G-protein-coupled receptors, orexin receptor 1 (Ox1R) and 2 (Ox2R). These receptors modulate diverse brain functions, such as sleep and metabolism, with their wide expression throughout the brain. Previous in vitro studies have found that Ox2R works in both Gq and Gi-coupled signaling pathways, indicating excitatory and inhibitory functions respectively. In vivo studies, however, the inhibitory role has yet to be discerned, whereas the excitatory function has been elucidated in numerous reports. Consequently, Ox2R is predominantly recognized for eliciting only excitatory signals in vivo.In this study, we found OxR2 expression in a subpopulation of Melanin-concentrating hormone-producing neurons (MCH neurons) characterized by several neurophysiological functions contrasting to orexin neurons. Electrophysiological recording from MCH neurons revealed instances of both excitatory and inhibitory responses to orexin B binding to Ox2R specifically, suggesting that Ox2R has an excitatory function in a subpopulation and inhibitory function in another subpopulation of MCH neurons. To investigate the physiological roles, we selectively ablated OxR2 in MCH neurons using a conditional knockout (cKO) system. These Ox2R cKO mice exhibited significantly reduced Non-REM to REM sleep transitions and impaired insulin metabolism in females, indicating MCH neuronal inhibition for sleep and activation for metabolism respectively. Conversely, Ox1R cKO mice did not show any phenotypes. Thus, Ox2R works within MCH neurons not only in the excitatory pathway to modulate sleep but also in the inhibitory pathway to modulate metabolism. OxR2 might engage both Gq and Gi-coupled proteins in distinct subpopulations of MCH neurons.