The Colts issued a release saying Thomas was hurt during Sunday's final practice, which was closed to the media. The team did not provide details of the injury but did say Thomas has been scheduled for surgery.
It's a big blow to the Southern Cal alum, who was smiling last Friday after his first workout with Indy.
But it could be an even bigger blow to the Colts, who must fill the void left by Marlin Jackson's departure. Jackson, Indy's first-round pick in 2005, signed with Philadelphia as a free agent in March.
Indy had big plans for the 6-foot, 192-pound cornerback, who was taken 94th overall in last month's draft.
"He certainly does have a very good pass defense skill set, where he can play man-to-man, which is something we've played a little bit more of than we have in the past," Colts coach Jim Caldwell said after selecting Thomas. "He's a guy who can walk up and pressure you a little bit and play some bump-and-run."
Thomas is the most recent loss to a Colts' secondary that has struggled to stay healthy in recent years.
Jackson tore the ACL in his right knee during practice in October 2008, costing him the rest of the season, then tore the ACL in his left knee during practice last November. Oft-injured Bob Sanders, the 2007 NFL defensive player of the year, missed all of training camp and the first five games last season after undergoing knee surgery. He made it back for just two games before tearing his left biceps and landing on injured reserve the same November day as Jackson.
Cornerback Kelvin Hayden also missed seven games last season because of injuries.
The absences gave two other rookies -- third-round pick Jerraud Powers and undrafted free agent Jacob Lacey -- a chance to make an impact last season. Both played big roles in helping the Colts win the AFC title and make their second Super Bowl in four seasons.
Colts president Bill Polian thought Thomas would follow the trend.
"He plays a lot like Lacey, similar in style, although he's taller and has good, long arms," Polian said on the second day of the draft. "He's a really good pass defender. ... Again, another need we felt that we had to fill, in terms of depth on the defensive side of the ball and felt good about doing it."
Instead, the second-team all-Pac 10 selection will now have to concentrate on rehabilitating his knee.
And it appears Thomas will not lose much, if any, money even though he had not yet signed his contract. He is covered by a standard league-wide insurance policy that ensures players receive an appropriate signing bonus and salary, based on their draft position, if they do get hurt in team activities.
But that won't make it any easier for Thomas, who did enough in his only season as a starter at Southern Cal to impress the Colts.
"I'm already motivated. They [the Colts] just threw wood in the fire. I'm ready to go," he said when asked whether he was ready for rookie minicamp. "For me to be on the same field as them, I feel all my hard work so far is appreciated. Now I'm ready to ball."