The winner of the game gets a playoff berth. The loser is out.
"One of the things I mentioned to the team today is, I said, 'Hey, guys, this is a playoff game. We've been in that mode since we were 1-5, so that's to our advantage,'" Colts first-year head coach Frank Reich said. "We've been playing this kind of football. We've been having this kind of mentality, we were forced into it. That was the bad thing, but the good that comes out of it is we had to embrace that mindset and take hold of that mindset."
Both teams are 9-6, but Colts quarterback Andrew Luck has owned the Titans since he entered the league. He is 10-0 against the AFC SouthDivision rival, but Luck noted this week that the past doesn't have any impact on this game.
"No, it doesn't matter," Luck said. "We talk about going 1-0 this week, the cycle starts over. What happened previously, what happened in previous years, it doesn't matter, what happened last weekend, it does not matter."
The Colts have climbed from a 1-5 hole to win eight of their last nine games for a chance to make the playoffs for the first time since 2014.
That run includes a 38-10 victory over the Titans on Nov. 18, when Luck completed 23 of 29 passes for 297 yards, three touchdowns and no interceptions.
Titans head coach Mike Vrabel and his team are not focusing on Luck's dominance over Tennessee, though.
"I don't think they are looking at that too much this week. I don't think so," Vrabel said. "I think they are looking at it as two good teams that are fighting to try to find a way to get into the playoffs. I don't think we can look at it any other way than that.
"We understand that he's a great quarterback. They've got good players and it will be a big challenge for us to try to defend them. For us on offense, it will be important for us to try to do a little better than we did last time against them."
Titans quarterback Marcus Mariota had to leave that game against Indianapolis in the second quarter with an elbow injury, and there are questions as to whether Mariota will play on Sunday.
Mariota was held out of Wednesday's practice, but still hopes to start Sunday's game.
"I just want to make sure we have the best option to win," Mariota said. "I'm going to do everything in my power to be available, so that when it's all said and done, if I'm able to be out there, I'm giving it my all. All I want is this team to win. However I can do that, however I can help, I'm going to find a way to do that."
The Titans will rely on their running game, with 6-foot-3, 247-pound running back Derrick Henry being the chief ball-carrier.
"He's so big," Colts rookie linebacker Darius Leonard said of Henry. "He's a huge guy and he's got great cut-back ability and his stiff-arm is pretty good. Just got to make him stop his feet. I think we will be fine from there."
Henry has rushed for 966 yards this season, with 492 of those yards coming in the past three games. But he had only 46 yards on nine carries in the earlier game against the Colts.
"There is no doubt we all know they want to run the football," Reich said. "I mean, (Henry) is an elite back, they run the football extremely well. They are good up front, so no doubt preparing to stop that running game is a big-time priority."
The Titans have won four in row, and their strength is their defense. Tennessee is second in the NFL in scoring defense, allowing just 18.0 points per game, and they have not yielded more than 16 points in any of their past three games.
However, defensive lineman Jurrell Casey, a four-time Pro Bowl pick and the Titans' best defensive player, suffered a knee injury against the Redskins and was placed on injured reserve.