Taylor is feared to have a high ankle sprain, a source told ESPN.
Taylor left the Colts' game against the Minnesota Vikings on Saturday during the first series and did not return.
Taylor has struggled with ankle soreness throughout the season, missing three games over a span of weeks in October and November. He had been slowly improving and seemed to have benefited from the Colts' bye in Week 14.
Now Taylor's frustrating season might be at its conclusion. He has a career-low 861 rushing yards through 11 games. He also has a career-low 4.5 yards per carry. Taylor was consistently impacted by the Colts' well-documented offensive struggles, including quarterback performance and offensive-line play.
The Colts were left to finish Saturday's game with a running back duo of Deon Jackson and Zack Moss. They combined for 37 carries, averaging 3.7 yards. Veteran Jordan Wilkins is on the practice squad and could be promoted to the active roster, if needed.
NFL Network first reported that Taylor sustained a high ankle sprain.