The Indianapolis Colts offense continues to show signs of being for real, and now they travel on the road for the first time this season when they go to Nashville on Sunday to take on the 0-2 Tennessee Titans.
The Colts' offense has been running heavily through a rookie, and I like him to continue to put up big numbers this week.
Find out who I like in my Colts vs. Titans predictions and NFL picks for Sunday, September 21.
Colts vs Titans prediction
Colts vs Titans Best bet: Tyler Warren Over 49.5 receiving yards (-114)
The leading target man for Daniel Jones and the Indianapolis Colts is first-round rookie tight end Tyler Warren. He has 11 catches for 155 yards on 16 targets through two weeks. He also has at least 76 yards in each of his two games.
The Colts have yet to punt the ball this season despite playing one of the better defenses in the NFL last week. Now they face a Tennessee Titans defense that ranks 27th in total yards allowed and 20th in passing yards allowed.
The Titans have not allowed much to tight ends in their first two games, but they also played two teams that do not have much to offer at tight end. They rank 18th in defending the short passing game, and the Colts use their tight ends in the short passing game much more than they use their receivers.
If Warren sees his usual eight targets in this game, then he should have no issue surpassing this yardage total. There is no reason to believe that he won’t unless Jonathan Taylor just busts out some huge runs early and they take such a big lead that it takes the passing game out. That is unlikely, though.
Colts vs Titans same-game parlay
To add to my best bet, I'm going to add Tyler Lockett to have fewer than two catches. The vet has been almost non-existent through two games, and I don’t expect him to get looks.
Also, we will add the Colts' moneyline, as they are just the much better team and should still be able to win a divisional road game.
Colts vs Titans SGP
- Tyler Warren Over 49.5 receiving yards
- Tyler Lockett Under 1.5 receptions
- Colts moneyline
Our big-ticket SGP: Jones in!
- Daniel Jones has all three rushing touchdowns for the Colts. The Titans have allowed three rushing touchdowns this season, and odds are good for Jones to add another.
Colts vs Titans SGP
- Tyler Warren Over 49.5 receiving yards
- Tyler Lockett Under 1.5 receptions
- Colts moneyline
- Daniel Jones anytime touchdown
Colts vs Titans game predictions
Colts vs Titans moneyline prediction
The Titans rank dead last in the NFL in rushing defense with a light box and 30th in defending runs inside the tackles. Meanwhile, the Colts rank first in the league on offense in both of those categories.
Colts vs Titans spread prediction
The Colts' spread is a little high for being a divisional road game, but they are clearly the better team right now, and the Titans could be one of the worst teams in the NFL.
Colts vs Titans Over/Under prediction
This Titans run game may get them enough points to contribute to this Over with a Colts offense that has yet to punt.
Colts vs Titans odds
- Spread: Colts +1.5 (-110) | Titans -1.5 (-110)
- Moneyline: Colts +100 | Titans -120
- Over/Under: Over 45.5 | Under 45.5
More NFL picks and odds from Covers
Colts vs Titans trend to know
The Colts have cashed the Over in 12 of their last 20 games. Find more NFL betting trends for Colts vs. Titans.
How to watch Colts vs Titans
| Location | Nissan Stadium, Nashville, TN |
| Date | Sunday, September 21, 2025 |
| Kickoff | 1:00 p.m. ET |
| TV | CBS |
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