Some stars might be out due to injury and others as a result of a suspension.
There are some who have been granted an extended holiday following a gruelling Euro 2016 or Copa America.
Others will be representing their countries in the summer Olympics in Brazil.
Arsenal have been hit the hardest but notable players will be absent for the other big clubs as well.
Who might your team be missing in the Premier League opener?
Check out our gallery above for more.