Notre Dame's first win over a ranked team this season cost the Irish (4-2) a starting linebacker and a respected receiver.
Linebacker Jarrett Grace broke the fibula in his right leg and receiver Daniel Smith suffered a fractured left ankle in Saturday night's 37-34 win over then-No. 22 Arizona State (3-2) in Arlington, Texas.
Coach Brian Kelly said Grace had surgery Sunday morning in Dallas and will be out four to six months.
"They put a rod in his leg for the fibula fracture," Kelly said during his Sunday teleconference. "He'll spend the next couple of nights there. Just talked to him, got off the phone. His spirits are good."
Brian Ratigan, Notre Dame's team surgeon, performed the surgery on Grace along with the Dallas Cowboys' team surgeon, Kelly said.
Kelly said, Grace will remain in Dallas until the threat of blood clots is gone and he can safely fly back to campus.
Grace was the Irish's leading tackler going into the game against the Sun Devils, and he had 40 tackles with one for loss before suffering the injury.
"Obviously a big loss for us, but we've got a senior in Danny Fox that will step in at that position," Kelly said. "Certainly you're losing somebody that we had counted on as a starter, so now you're deep into your depth and that wasn't an area with a lot of experience.
"Kendall Moore is going to have to obviously play. (Joe Schmidt) is going to have to play for us. So those guys are going to have to be counted on now. We'll obviously look at (freshman) Michael Deeb. So those three guys, we'll have to activate them on the bye week and start to consider all three of those guys in terms of being in the gap."
Smith is scheduled for surgery later this week after the swelling in his ankle goes down, Kelly said. The senior receiver from South Bend's Clay High School had one catch for nine yards this season and had eight catches for 56 yards in 26 games in his career.
"It was pretty emotional at halftime, we mentioned Danny at halftime," Kelly said. "There was a lot of emotion in the locker room. I usually don't use a 'Win one for the Gipper' talk, and I don't want to equate it in those terms, but generally speaking, we talked about losing Danny and in particular that he probably wasn't going to play again. There was a lot of emotion in the locker room because they love Danny Smith and what he has done for our program as a dedicated player for Notre Dame.
"He loves Notre Dame, and we have seen him grow as a person and player, and he is going to be sorely missed. I would say that his impact is a local player that was on a 12-0 undefeated regular-season team, and he has left an impact on our younger receivers as to how to work every single day and how to handle himself both on and off the field."
Notre Dame has this week off before returning to play host to USC in a 7:30 p.m. game Oct. 19.
Kelly said the Irish will use the bye week to rest veterans and get some younger players more work.
One veteran that will be getting some rest is defensive end Stephon Tuitt, who had surgery in the offseason to repair a sports hernia and is still feeling the affects from the procedure.
"He needs rest," Kelly said. "I've said this before the surgery he had has affected his back, it's affected hip flexors. He's really struggled. Some people dismiss it and say, 'Well, you know, you just had minor surgery.' Well, it's affected a lot of things. He's really struggled all week with back tightness. He missed a day of practice because his back locked up.
"We got to be careful with Stephon. This week, we will work on technique, but we are going to make sure he is healthy for us going into USC."