SummaryDifferent mouse strains used in biomedical research show different phenotypes associated with their genotypes. Two mouse strains commonly used in biomedical sleep research are C57Bl/6 and C3H/He, the strains differ in numerous aspects, including their ability to secrete melatonin as well as the expression of several sleep‐related genes. However, sleep regulation has only limitedly been compared between C3H/HeN and C57Bl/6 mice. We therefore compared sleep–wake behaviour and EEG‐measured spectral brain activity for C57bl/6 and C3H/HeN mice during a 12:12 h light: dark baseline and during and after a 6 h sleep deprivation. The C3H mice spent more time in NREM sleep around the light–dark transition and more time in REM sleep during the dark phase compared with C57bl/6 mice. The C3H mice also showed more EEG activity in the 4.5–7.5 Hz range during all stages and a stronger 24 h modulation of EEG power density in almost all EEG frequencies during NREM sleep. After the sleep deprivation, C3H mice showed a stronger recovery response, which was expressed in both a larger increase in EEG slow wave activity (SWA) and more time spent in NREM sleep. We show large differences regarding sleep architecture and EEG activity between C3H and C57bl/6 mice. These differences include the amount of waking during the late dark phase, the 24 h amplitude in EEG power density, and the amount of REM sleep during the dark phase. We conclude that differences between mouse strains should be considered when selecting a model strain to improve the generalisability of studies investigating biomedical parameters related to sleep and circadian rhythms.