We have previously reported a larger and more prolonged increase of slow wave activity (SWA) in NREM sleep after sleep deprivation (SD) in prion protein deficient mice (PrP) compared to wild-type mice. Regional differences in the SWA increase were investigated by comparing the effect of 6 h SD on a frontal and occipital derivation in PrP deficient mice and wild-type mice. The larger increase of SWA after SD in PrP deficient mice was restricted to the occipital derivation. The difference appeared after the waking-NREM sleep transitions, making it unlikely that PrP is involved in the mechanisms enabling the transition to sleep. Our findings may reflect differences between the genotypes in the need for recovery in this particular brain region.