<p>Epidemiological studies have revealed a bidirectional functional relationship between chronic sleep deprivation and the development of obesity. However, it remains unclear whether these factors can potentiate each other’s damaging effects on neurophysiological functions. The aim of the present study was to investigate the combined effects of a high-fat diet (HFD) and chronic sleep deprivation on the characteristics of sleep and destructive changes in the locus coeruleus in male Wistar rats. HFD supplementation for 10 weeks was found not to result in changes in the organization of the sleep–waking cycle as compared with control animals given standard chow (SC). However, during sleep restriction (SR) in a polyphasic regimen of 3 h of wakefulness and 1 h of sleep opportunity using a rocking platform for 5 days, the compensatory increase in slow-wave activity in response to sleep loss during 1-h rest periods was less marked in rats on the HFD than in rats receiving SC. During the recovery period, a decrease in the proportion of deep slow-wave sleep (SWS) was found in both groups, though this indicator reached the initial level by 14 days in rats on SC, while this did not happen in rats on the HFD. SR was found to be accompanied by the death of neurons in the locus coeruleus; the combination of HFD and SR increased neurodegeneration. Thus, these studies provided the first demonstration that chronic SR combined with an HFD leads to marked disturbances in the homeostatic mechanisms of regulation of SWS with subsequent deterioration in sleep quality, which could be a consequence of progressive dysfunction of the noradrenergic system of the locus coeruleus.</p>