Is there any biological reason for humans to rest after x days of work? A lot of people live in a 7 day cycle, where 5 days of work are followed by 2 days of "rest". Vacations and holidays can increase the time available for resting. **Is there any biological reason for humans to rest after x days of work?** Can this be explained by the buildup of by-products of metabolism, like Homocysteine?

I think your main assumption is not true -- we do not really rest on weekends.

I do not know many people who only rest on weekends. Usually this is the time for socializing, doing home-related work, physical activity (sports, hiking), spending time with your kids, all of which is often almost the opposite of a rest.