Strongside linebacker A.J Klein (knee) and middle linebacker Kiko Alonso (thigh) were both injured during last Thursday's win at Atlanta. The timing is especially unfortunate because the 49ers have the NFL's No. 2-ranked rushing offense at 148.0 yards per game.
And because both teams are 10-2, Sunday's game could wind up determining the NFC's top seed and home-field advantage.
The Saints' run defense, meanwhile, ranks No. 3 in the league, allowing just 88.6 yards per game. They will likely count on veteran backup Craig Robertson as one replacement starter. Backups Stephone Anthony and newly signed Manti Te'o could also help fill the void.
On a positive injury note, the Saints' standout left tackle Terron Armstead is listed as questionable after he returned to practice on a limited basis all week with his ankle injury. Even if he is not ready to return yet Sunday, it's a good sign that he will be back soon.