The median preoptic nucleus (MnPO), part of the anteroventral third ventricular region, plays a key role in body fluid homeostasis and cardiovascular regulation. Recently, a cluster of neurons showing sleep-related c-fos immunoreactivity was found in the rat MnPO, and a subsequent electrophysiological study found that nearly 76% of rat MnPO neurons exhibit increased discharge during sleep. In a recent single unit recording study in mice, we found that sleep-active neurons are not localized in any specific region of the preoptic/basal forebrain (POA/BFB). However, the discharge profiles of mouse MnPO neurons across wake-sleep states remained to be determined. In this study, we therefore examined whether the mouse MnPO contains a high proportion of sleep-active neurons and constitutes a distinct cluster of sleep-promoting neurons in the median preoptic region. We recorded a total of 234 single units in the MnPO, the laterally adjacent peri-MnPO, the dorsally adjacent medial septum (MS), and the ventrally adjacent periventricular (Pe)/medial preoptic (MPO) area (Pe/MPO). We found that the MnPO contained similar proportions of sleep-active (31.9%) and waking (W)-active (33.0%) neurons, together with many waking/paradoxical sleep (W/PS)-active neurons (23.4%), whereas the Pe/MPO and MS contained a high proportion of sleep-active neurons (66.0 and 62.9%, respectively), while the peri-MnPO contained a high proportion of W-active neurons (57.1%). In the MnPO, both W-active and W/PS-active neurons were distributed throughout the nucleus, whereas sleep-active neurons were mostly located on its border. Only slowly discharging (<5 Hz) slow-wave sleep (SWS)/PS-selective neurons were found in the MnPO. During the transition from W to SWS, all of these SWS/PS-selective neurons fired not before, but after, sleep onset, with a gradual increase in discharge rate. In addition to its well-known homeostatic and cardiovascular functions, the MnPO might modulate the sleep-waking cycle by playing different roles in sleep/wake state regulation.