The pair picked up muscle injuries in their 2-0 victory over Basel on Wednesday that sent them into the Champions League knockout stage for the second consecutive season.
"We are smiling but we will not be celebrating," Schalke sports director Horst Heldt told reporters, aware that Schalke's domestic run has not been stellar.
Keller's team has crashed out of the German Cup and dropped to sixth in the Bundesliga, putting his job at risk. Wednesday's result no doubt gave him a new lease of life.
A win over Freiburg would most likely see him reach the winter break still in the job.
"A huge weight has been lifted off our shoulders," Keller said. "But there will be peace and quiet only until Sunday. The pressure here is huge. Not just on me but also on the team."
Keller will have to reshuffle his team ahead of Freiburg to compensate for the absence of Draxler, who scored Schalke's first goal on Wednesday, and Hoewedes.
"We have had bad luck with injuries. I will have to see which 11 players I can get together," said Keller, who is already missing striker Klaas-Jan Huntelaar and central defender Kyriakos Papadopoulos, among other.
There is some consolation with Jermaine Jones, suspended against Basel, back in the team and Heldt sounded upbeat.
"We now need to recover. It is of course frustrating that Draxler and Hoewedes could be out for the last two games because we have had a bad run with injuries."
"But I am sure we will able to get the job done and find the solutions to fill the gaps."
Their opponents, Freiburg, have won just twice this season, battling to avoid relegation after last season's success and Europa League qualification saw several key players poached by bigger clubs.
Bayern Munich will make sure they will go into the winter break in top spot with victory over struggling Hamburg SV, having opened up a four-point lead from second-placed Bayer Leverkusen, who host Eintracht Frankfurt on Sunday.
(Editing by Amlan Chakraborty)
