Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas.

NPS binds specifically to a newly de-orphaned G protein-coupled receptor, NPSR. Animal studies show that NPS suppresses anxiety and induces wakefulness and displays significant role in the extinction of conditioned fear.

The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic. Several peptide derived NPS agonists and antagonists have also been developed.