J.J. Watt broke his left leg on Sunday night against the Kansas City Chiefs, leaving the Houston Texans without one of their biggest stars for the second straight season.
The team announced that he sustained a tibial plateau fracture.
The three-time Defensive Player of the Year returned this season after missing the last 13 games of last season after his second back surgery. He played every game in his first five seasons in the NFL before his injury last year.
"I feel terrible for the guy," O'Brien said. "But ... just knowing him and knowing the type of guy that he is, he's an amazing human being. And he will work extremely hard to be back to play for this football team. I know that."
Houston linebacker Whitney Mercilus was also injured in the first quarter and was ruled out with a chest injury. O'Brien said he was concerned about his injury, but did not provide any further details on it after the game.
Veteran cornerback Johnathan Joseph said it was difficult to see two key members of the defense go down on the same drive.
"You think about it because obviously you're human and you feel for the guy and it's obviously a loss and it makes you do different things on defense," he said. "But at the end of the day you've got to continue to play. It's got to be the next guy up mentality you've got to always have ... I'm not saying we're going to replace J.J.'s level of play but the next guy's got to step in and pick it up."
Watt was injured while being blocked midway through the first quarter and fell to the ground.
The defensive end remained on his hands and knees for a couple of minutes while trainers checked on him. They flipped him onto his back and were looking at his left leg. He was then helped to his feet and looked to be in a lot of pain and didn't appear to be able to put any weight on the leg as he was helped off the field by two Texans officials.
He remained on the sideline under a tent for a few minutes before being taken to the locker room on a cart.
About 30 minutes later, television footage showed Watt walking on crutches to an ambulance before sitting on a stretcher, being moved into the ambulance and taken away.
The 28-year-old Watt had 15 tackles this season, but didn't get a sack in five games. He had 1-1/2 sacks last season, after leading the NFL with 17-1/2 sacks in 2015 and finishing second in 2014 with 20-1/2.
The Texans know that it's a big blow to lose a player of his caliber again, but they have to figure out a way to move on like they did last year when the defense allowed the fewest yards in the NFL despite his absence.
"He's a big piece, but ... you've still got to step up and play," nose tackle D.J. Reader said.
"Somebody's got to go out there and play. Nobody feels sorry for you. The other 31 teams in the league don't feel sorry for you."