NFL: Tennessee Titans at Indianapolis Colts
Thomas J. Russo / USA TODAY Sports

Two AFC South teams square off this Sunday, as the Indianapolis Colts travel to Nashville to take on the Tennessee Titans. The winless Colts have a quarterback question as Carson Wentz sprained both of his ankles during the 27-24 loss to the Los Angeles Rams last week. It's unknown if he will suit up in Week 3. As for the Titans, they are coming off of an emotional comeback overtime win against the Seattle Seahawks. The reigning rushing champ Derrick Henry rushed for 182 yards and three touchdowns.

These two teams are considered to be the favorites to win the AFC South, but both haven't lived up to expectations just yet. We could learn a lot about these two clubs in Week 3. Are the Colts ready to earn that first win, or are the Titans destined to win two in a row?

The Titans and Colts have split their season series two years in a row now. Before we get into this matchup, here's how you can watch on Sunday. 

All NFL odds are via Caesars Sportsbook.

How to watch

Date: Sunday, Sept. 26 | Time: 1 p.m. ET
Location: Nissan Stadium (Nashville, Tennessee)
TV: 
CBS | Stream: Paramount+ (click here)
Follow: CBS Sports App
Odds: Titans -5, O/U 48

Key matchups to watch

Colts quarterbacks

If Wentz doesn't play, you can't feel too great about the Colts' chances. Tom Pelissero of the NFL Network reported that Indy could play two quarterbacks if Wentz is out in Brett Hundley and Jacob Eason. Running a two-quarterback system with a second-year backup and a journeyman who hasn't started since 2017 sounds like a bad game plan. Indy's offense hasn't been great through two contests, as it has averaged just 20 points per game (tied for No. 25 in the league). If Wentz does start -- which is very possible -- you have to wonder how healthy he really is and how he will look moving around. He says he's "throwing the kitchen sink at it" in trying to get back to full speed. 

Michael Pittman vs. Titans secondary

Pittman was a player many tabbed as a breakout candidate in 2021, and the second-year receiver out of USC had his first big game in Week 2. He led the Colts in receiving with eight receptions on 12 targets for 123 yards. He has only one other 100-yard game, and that came against the Titans last year. 

If you had to point to a weak spot on this Titans defense, it's the secondary. DeAndre Hopkins and Tyler Lockett feasted on Tennessee's cornerbacks in the first and second games of the season. Making Pittman a major part of the game plan could be a key to victory. 

Derrick Henry vs. Colts D

Henry carried the Titans to a win last week with three second-half touchdowns -- including a 60-yard score. Usually when a team reels off a comeback facing a double-digit deficit in the second half in a hostile environment, it relies on the pass game. Not for the Titans. Henry can score anytime he touches the ball, and will continue to be Tennessee's bell cow. He also rushed for 178 yards and three touchdowns the last time he faced the Colts. Stopping Henry or just limiting him is the Colts' best chance for a win. 

Prediction

Latest Odds: Tennessee Titans -5

It's hard not to pick the Titans in this spot. I think last week's win can spark a bit of a winning streak. Henry is rolling, Julio Jones had his first big game as a Titan last Sunday and it's Houston Oilers week in Nashville. Nearly 80 former players will be in attendance to provide a raucous environment.  

Pick: Titans 30-21 over Colts

Check out CBSSports.com for even more predictions on this game and the rest of Week 3.