Pierce had been working his way back from offseason ankle and heel surgery and was cleared to play without an injury designation entering Sunday. He had one catch for 11 yards before leaving the game.
The game was tied 10-10 in the second quarter when Pierce left the field.
An injury occurred late in the first quarter while Pierce was running a route. He planted his left leg and tried to change direction toward the sideline, and his ankle appeared to bend awkwardly. He struggled to put weight on the leg and was eventually taken to the locker room on a cart.
The injury involves the same left ankle Pierce underwent surgery on during the offseason. He spent much of the offseason recovering before returning for the start of the regular season.
Pierce entered the game after posting four receptions for 61 yards on six targets in Week 1 against the Baltimore Ravens. He had been expected to take on a larger role against Kansas City after playing only 32 offensive snaps in his first game back from surgery.
The Colts will monitor Pierce and determine the next steps based on his latest injury.
