McFarland hurt the patella tendon Friday and missed Saturday's controlled scrimmage after an MRI showed the extent of the injury, the team said.
Colts coach Tony Dungy called the injury serious and that it might need surgery but did not give details on how it happened.
"It's a long-term injury," Dungy said. "It's (surgery) something that we're contemplating. It's something that I think is going to happen.
Morris returned to practice Monday, and Mathis was expected back soon, but not McFarland.
"He's not going to be back in the next three or four weeks or anything like that," Dungy said.
Raheem Brock will start at one defensive tackle spot, but it was unclear who would eventually take over McFarland's role.
Rookie defensive tackle Quinn Pitcock, a third-round draft pick from Ohio State, could fill in. Pitcock practiced for the first time Monday after missing the first week of camp with a leg injury. Dungy also said rookie defensive end Keyunta Dawson will get a look.
Dawson, a seventh-round pick, has seen some work at defensive tackle in camp and was impressive in the controlled scrimmage, with two sacks, a forced fumble and a recovered fumble.
Dungy also did not rule out trying to find another defensive tackle on the NFL's waiver wire or through a trade. But he said the team would rather look at its own roster for help.
"We won't leave any stone unturned. But for the most part, guys that are here are the guys that we're counting on," Dungy said.
Brock said it's up to the younger players to fill in.
"That's what we've got to do. When somebody gets hurt, another guy has to step up," Brock said.
Copyright 2007 by The Associated Press