Ajayi exited last week's game against the Tampa Bay Buccaneers after suffering a back injury, and Philly went on to lose 27-21. He rushed for 23 yards and a touchdown before exiting, and in two games this season, he has registered 85 yards and three scores on the ground.
Last year, the 25-year-old rushed for 873 yards and a touchdown during the regular season. He split time with the Miami Dolphins and Eagles and was an instrumental part of the latter's Super Bowl run.
Sproles did not play last week, and in one contest this season, the 35-year-old veteran has rushed for 10 yards and caught four balls for 22 yards. He also returned three punts for a total of 29 yards in Week 1.
After missing all but three games last season due to injury, Sproles decided to return in 2018 for one final season.
With both Ajayi and Sproles on the shelf for Week 3, second-year running back Corey Clement will likely be the bell cow against Indy.
Clement totaled 444 yards and six touchdowns from scrimmage as a rookie, and this far in 2018 he has rushed for 56 yards and a score, while catching five passes for 55 yards.
Aside from Clement, look for Wendell Smallwood and undrafted rookie Josh Adams to get some looks against the Colts as well.