The centre-back will play no part in the Bundesliga side's opening UEFA Champions League fixture at Stamford Bridge due to a hip problem.
Howedes joins the likes of Leon Goretzka (hamstring), Jefferson Farfan (knee) Fabian Giefer (adductors) and Sead Kolasinac (knee) in a busy Schalke treatment room.
Schalke coach Jens Keller was understandably disappointed to lose the 26-year-old, who was a member of Germany's World Cup winning team, for such an important clash but he still plans on playing with four in defence.
"Losing the captain doesn't make things easier," Keller said. "We will play with four at the back, but we haven't got many options."
Full-back Dennis Aogo urged the team to rally in Howedes absence, while noting that Chelsea have improved since they met the Premier League side in last season's group stage.
"Losing Howedes is no easy situation but we will have to try and compensate for it," he added.
"Compared to last season they [Chelsea] are even a bit stronger. They boast enormous quality, especially going forward."
