Austrian full-back Fuchs has played 90 minutes for Austria against both Germany and the Republic of Ireland over the past week and has returned to Gelsenkirchen with an injury, while Brazilian central defender Santana is sick.
Meanwhile, Dutch striker Klaas-Jan Huntelaar remains unavailable for selection due to the knee injury he sustained in Schalke's 4-0 loss to Wolfsburg on August 17.
"We can't really tell yet (who will play against Mainz), Christian Fuchs came back with slight injury, he trained a bit but couldn't finish," Keller said.
"Then Felipe Santana has come down with the flu, we have to wait now.
"Klaas-Jan is still not an option for Saturday, other than that, everyone else came back from the internationals fit and healthy."
Schalke will enter Saturday's game at Mainz's Coface Arena in 13th spot on the Bundesliga table with just three points from four rounds.
The North-Rhine Westphalia club lost their opening three games of the Bundesliga season before they overcame Bayer Leverkusen 2-0 before the international break.
By contrast, Mainz sit fifth on nine points with three victories and Keller knows what to expect from Thomas Tuchel's energetic side.
"They will be very aggressive for the first 20 minutes, they will attack from the front, they will show a huge amount of effort," Keller said.
"Tactically they have improved and have good ideas around their team."
Schalke have a busy period coming up with seven games in three weeks, including two UEFA Champions League matches and a DFB Pokal tie.
But Keller would not have it any other way and cannot wait to lead Schalke in the Champions League.
"We wanted to reach a stage where we can play international matches during the week and that's what we have done," Keller said.
"We are looking forward to hearing the Champions League hymn on a Tuesday or Wednesday evening, I think every player wants that."
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