The Indianapolis Colts proved their offense was no fluke in Week 1 and now get to face a mediocre defense when they travel for the first time this season to take on the Tennessee Titans on Sunday, September 21.
My early Colts vs. Titans predictions and NFL picks expect the Indianapolis offense to continue rolling.
Colts vs Titans predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Early Colts vs Titans spread pick: Colts -3.5
After a historic performance in Week 1, Daniel Jones and the Indianapolis Colts offense were largely expected to come back down to Earth against a vaunted Denver Broncos defense. Instead, Jones threw for 316 yards with no turnovers, and the Colts put up 473 total yards in a 29-28 win.
The Colts are currently fourth in scoring and second in total yards gained through two weeks, and I don’t think anyone expected this kind of performance from Jones. Now, he gets a Tennessee Titans defense that has allowed 756 total yards and 53 points in two weeks.
The Titans have also struggled mightily against the run, ranking dead last in rushing defense with a light box and 30th in defending runs inside the tackles. Meanwhile, the Colts rank first on offense in both categories.
The Colts defense had its struggles last week, but it did force a ton of turnovers in Week 1 against the Miami Dolphins and kept them off the scoreboard until late. The Titans might be one of the worst teams in the NFL, and this is a low spread, even for a divisional road game.
Early Colts vs Titans total pick: Over 43.5
After two weeks of closely watching the Colts, I have a feeling we are going to get a lot of Overs this season. Obviously, they went Under in Week 1 because of how much they shut down the Dolphins, but most games where you score 33 points will lead to an Over.
They allowed 324 total yards and 28 points to the Broncos, including 118 yards on the ground. The Titans offense was anemic in Week 1, but they showed some life on the ground in Week 2, as Tony Pollard had 92 yards on 20 carries.
Last year, Pollard had 128 yards on the ground on 25 carries in his two matchups with Indy. I do not expect the Titans to move the ball freely, but they should get enough yards to score on occasion and get several field-goal opportunities.
That should be enough of a contribution for this Over to hit. I would expect the Colts to once again be around the 30-point mark, and it would be hard for me not to like the Over if that happens again.
Colts vs Titans odds
- Colts vs. Titans spread: Titans +3.5
- Colts vs. Titans moneyline: Colts -184, Titans +154
- Colts vs. Titans Over/Under: 43.5
How to watch Colts vs Titans
- Colts vs. Titans matchup
- Date: Sunday, September 21, 2025, 1:00 p.m. ET
- City: Nashville, TN
- Venue: Nissan Stadium
- TV: CBS
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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