It will be the first time that former Colts quarterback Peyton Manning has faced his old team since his departure in 2012.
The top pick from last year's Draft told the team's website: "I don't think there's any problem for anybody keeping focused. It's a football game. We're not ignorant. We know who's coming to town. We know it's a great football team and a great challenge for us, a great opportunity for us.
"I don't think there will be any problem keeping focus this week. I never viewed it as replacing Peyton. I just viewed it as an opportunity to play quarterback in the NFL. It just so happens one of the greats of all-time was here before me.
"I had an opportunity to go to his camp when I was in eighth grade, then as a college counselor for a couple of years in school. He's always been very helpful and kind. They're such a classy family. It's fun to know them."
Manning has completed 2,179 passing yards and 22 touchdown passes during the first six games of the season.