Background/Aims: This study aimed to investigate the possible association of regional cerebral perfusion and sleep loss in Alzheimer’s disease (AD). Methods: 55 AD patients were characterized as having (SL) or not having (NSL) nocturnal sleep loss based on standard AD scales assessing sleep over the previous 4 weeks. 99mTc-ethylcysteinate dimer SPECT scans were performed in a relaxed, wakeful state. Whole-brain analysis using Statistical Parametrical Mapping (SPM5) was performed to compare perfusion across groups. In addition, the AD groups were compared to normal control (NC) subjects of comparable age and gender to provide a context for interpretation of findings. Results: SPM analysis showed increased perfusion in the right middle frontal gyrus (R-MFG, Brodman area 9, p = 0.016, familywise-error-corrected) in SL versus NSL patients. Comparison with NC subjects confirmed that perfusion in the R-MFG among SL patients did not exceed that found in NCs (relative rather than absolute hyperperfusion). Conclusions: In this sample of mild-to-moderate AD patients, relative hyperperfusion in the R-MFG is associated with reports of SL. This region may play a role in regulating sleep.