Abstract Pro-opiomelanocortin (POMC) immunoreactive (-ir) neurons in the brain are confined to the arcuate nucleus (ARC) in the hypothalamus (1) and the commissural nucleus tractus solitarius (cNTS) in the medulla (2). POMC-derived peptides have been shown to influence homeostasis via connectivity with brainstem nuclei that influence cardiovascular function, respiration and nociception. We have utilized anterograde tracing with phaseolus vulgaris leucoagglutinin (PHA-L) to identify ARC and cNTS efferents and their terminal fields in the brainstem to provide neuroanatomical data on the function of these POMC systems. ARC neurons were shown to innervate midline brainstem nuclei, particularly the raphe complex, periaqueductal gray (PAG) and NTS. In contrast, cNTS putative terminal fields were identified in lateral brainstem nuclei, particularly catecholaminergic groups. Both nuclei innervate the lateral parabrachial nucleus (LPB) and nucleus locus coeruleus (LC). This terminal field distribution indicates that the ARC and cNTS may influence autonomic function via overlapping connectivity with the LC and LPB, whereas sensory homeostasis is maintained by ARC to PAG and raphe innervation, as well as cNTS to lateral brainstem connectivity.