Mack will undergo more tests to determine whether he needs surgery and how long he will be out, but he will not play Thursday night against the Texans, per the source.
Mack was having his best game since Week 5 at Kansas City before getting hurt early in the third quarter. He had rushed 14 times for 109 yards, including four runs of at least 10 yards before the injury.
It's uncertain how Mack injured the hand.
Jonathan Williams became the Colts' primary running back after Mack left the game and will likely start against the Houston Texans on Thursday, with Nyheim Hines backing him up. Williams, who went into Sunday with just 1-yard rushing on the season, rushed for a career-high 116 yards against the Jaguars.
Williams and Mack are the first two Colts running backs to rush for at least 100 yards in the same game since Randy McMillan and Albert Bentley did it on Oct. 6, 1985.