Brazil left-back Marcelo has fractured a bone in his right foot and is expected to be out of action for up to three months, while Fabio Coentrao, Alvaro Arbeloa, Karim Benzema, Gonzalo Higuain and Sami Khedira are all in need of treatment.
Left back Coentrao dropped out of the Portugal squad with a muscle complaint, and with the versatile Arbeloa also being substituted out of Spain's 1-1 home draw against France with a muscle problem, Jose Mourinho may have gaps to fill at full back in upcoming games.
"It looks pretty black," Spain and Real midfielder Xabi Alonso said.
"It's really bad luck that in seven days we have lost all three (full-backs). I am sure the boss is working on finding a solution."
Khedira missed Germany's 4-4 draw at home to Sweden after picking up a muscle injury against Ireland.
Forward Higuain suffered a knock to his ankle while helping Argentina to a 2-1 win in Chile, while his strike partner Benzema hobbled out of France's draw at the Calderon clutching his left knee.
"I hope it only looks bad and that we haven't suffered any bad luck with the strikers," Alonso added.
"I hope they will both be ready for Saturday."
The Spanish champions host promoted Celta Vigo on Saturday as they look to close the eight-point gap on leaders Barcelona.
The Champions League Group D leaders return to European action next Wednesday at Borussia Dortmund, who are two points behind them in second place.