Howedes was withdrawn in the 58th minute of Schalke's UEFA Champions League last 16 second leg clash at the Bernabeu, which Schalke lost 3-1 as the Bundesliga outfit slumped to a 9-2 aggregate defeat.
Schalke will now turn their attentions to domestic concerns following their elimination from European competition, with Keller's men still not secured of a place in the top four of the German top flight.
But coach Jens Keller revealed that they are likely to be without skipper Howedes on Saturday, although the club are awaiting the results of scans.
"Benedikt Howedes' injury is frustrating," Keller said. "We don't have a clear diagnosis yet and have to wait on an MRI scan.
"It's something muscular, in any case. He probably won't be able to play against Eintracht Braunschweig."
Despite Schalke's Champions League exit, Keller expressed satisfaction with his side's display. However, he did concede that his charges made too many errors.
"We're disappointed to lose, of course, but despite that I'm very pleased with my team's performance," Keller added.
"They tackled strongly, kept running and worked tightly together. It's clear that you can't completely shut down Real without them having a couple of goalscoring opportunities.
"The only frustrating thing was making two errors after 75 minutes that led to us conceding two goals. Nevertheless, the team reacted well after the first leg defeat."
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