Midifelders Blaise Matuidi, Yohan Cabaye and Maxime Gonalons, as well as centre-back Laurent Koscielny, will miss the Spain game if they are booked on Friday.
Asked if he may decide to do without some of the regulars to protect them from suspension, Deschamps told a news conference: "That is a possibility but that doesn't mean I will do it.
"The risk of suspension is an extra danger. Freshness is important when you are playing two teams with completely different profiles, and I have to take into consideration that I have four players who could be suspended [for the Spain game] and three of them in midfield."
Matuidi has been in terrific form with Paris Saint-Germain this season and his omission might be too big a gamble, but Deschamps could rest Cabaye and give Juventus midfielder Paul Pogba his first cap.
Pogba possesses a powerful shot and is capable of scoring goals from distance which could be a useful asset against a team who will defend deep.
"They will come to the Stade de France with a very defensive mindset," said Deschamps. "We will need to find solutions."
Pogba would be happy to provide one.
"If the coach thinks I'm ready, I'm ready," the 20-year-old told a news conference.
France are second in their qualifying Group I behind with seven points from three games, behind Spain on goal difference.
Spain are sure to test the French defence and Deschamps may be willing to protect the Mamadou Sakho-Laurent Koscielny pairing by resting the Arsenal centre back.
Young Real Madrid defender Raphael Varane could start on Friday.
"There is always a risk," said Deschamps.
"But at some point he will have to start a game. Given his performances with Real, I'm not worried, although playing an international game with France is still another level.
"I think he can meet expectations."
Varane, 19, has been called up twice by Deschamps but each time had to leave the squad due to injury.
