The Tennessee Titans will have their hands full in Week 3 with an AFC South battle against the Indianapolis Colts at Nissan Stadium. 

Tennessee once again enters the game as the underdog against a Colts team that has been one of the bigger surprises in the NFL at the outset of the 2025 regular season. Playing behind a rejuvenated Daniel Jones at quarterback, the Colts are off to a hot 2-0 start after dismantling the Miami Dolphins in Week 1 and squeaking out a hard-fought victory against the Denver Broncos in Week 2. 

Heading into this week, the Titans are facing an uphill battle dealing with inconsistencies and injuries, and are battling to right their ship after opening the season against two of the best defenses in the league. While they have flashed some potential in their two losses, there have been too many miscues to overcome. 

Will this week be any different? Here are five key matchups to keep an eye on that could play a pivotal role in deciding the outcome. 

Titans’ offensive line vs. Colts’ attacking defense

The Titans’ offensive line has struggled early in the 2025 season and faces some major question marks heading into this battle with the Colts, with both JC Latham and Kevin Zeitler ailing. Now they head into Week 3, having to prepare for the aggressive style of a Lou Anarumo brand of defense. 

Known for being creative in his schemes, Anarumo’s defense will pose significant problems for a unit that has allowed 11 sacks through two weeks of action. 

Titans’ defense vs. Colts’ rushing attack

The Colts have a formidable rushing attack led by Jonathan Taylor, and come into the matchup third in the league, averaging 161.5 yards per game. Taylor is explosive and healthy, and the former NFL rushing champion appears well on his way to another outstanding season. 

The Titans’ rush defense has been a mixed bag through two weeks of action, and they have been susceptible to giving up explosive plays. Tennessee currently ranks 29th in rushing defense and must improve if they are going to have a chance.  There is a chance T’Vondre Sweat is back in the middle, which will be a boost for the struggling unit.

Tony Pollard vs. Colts defense

Pollard had an outstanding game against the Los Angeles Rams, rushing for 92 yards on 20 carries, and has been the most consistent part of the Titans’ offense through two weeks of action. 

The Colts’ defense has been vulnerable against the run early in the season, and it would be wise for the Titans to focus on that in their game plan, allowing rookie quarterback Cam Ward to build off that foundation. 

Calvin Ridley vs. Broncos’ secondary

During the preseason, the combination of Ward and Ridley looked like they were going to be a problem for opposing defenses. Unfortunately, that has not translated to the regular season. With Elic Ayomanor starting to flash his potential, this could be the week that the preseason chemistry flashes. 

Tennessee needs Ridley to prove he is its top receiver. The Colts have a stout defense, but there should be opportunities for the star wideout to make plays. 

Titans pass rush vs. Daniel Jones

Jones appears rejuvenated since joining the Colts and looks much more comfortable in this offense. In fact, he has had nothing but success through two weeks of action. Incredibly, the Colts have not been forced to punt in 2025. This level of success is not sustainable, and at some point, Jones will falter. 

The Titans have struggled to pressure quarterbacks during the first two weeks of the season and must turn that around against the Colts. If they can make Jones uncomfortable, they can force mistakes like they did in Week 1 against Bo Nix and the Denver Broncos.