Defender Hoewedes and former Real striker Huntelaar picked up knocks in Saturday's 3-1 Bundesliga win at home to Hoffenheim along with midfielder Marco Hoeger and forward Eric Maxim Choupo-Moting.
"Who will be able to play will be decided after the final training session," coach Roberto Di Matteo told a news conference on Monday.
Even without their injury problems, and midfielder Kevin-Prince Boateng's suspension, Schalke would be facing a formidable task at the Bernabeu after losing 2-0 to the holders in last month's last-16 first leg in Gelsenkirchen.
Real have stumbled recently in La Liga, losing top spot to Barcelona at the weekend after a 1-0 reverse at Athletic Bilbao, but should have little trouble getting past the Bundesliga side.
Victory for Carlo Ancelotti's men would equal the Champions League record for consecutive home wins (12) and break the record for the most in a row overall.
Real matched Bayern Munich's competition-best run of 10 straight victories at Schalke.
"We have to have a perfect day as a team and hope our opponent is not on super form," said Di Matteo who was coach of Chelsea when they won the 2012 Champions League.
"If we manage to get the first goal it will certainly be very, very interesting. The important thing is that we are solid and organised as a team.
"If we manage that we can dampen Real's attacking power."
(Reporting by Iain Rogers, editing by Tony Jimenez)
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