Titans vs. 49ers Prediction, Odds, Spread, Trends for NFL Preseason Week 1

Week 1 of the NFL Preseason will begin on Thursday, and the final game of the night is an interconference showdown between the Tennessee Titans and the San Francisco 49ers.

The Titans are hoping the Robert Saleh era will help move them in the right direction after a disappointing 2025 season with new quarterback Cam Ward. Meanwhile, the 49ers are hoping they can leave an injury-riddled 2025 campaign behind them and get back to competing for a Super Bowl.

Let's dive into the odds and my best bet for Thursday's night's preseason showdown.

Titans vs. 49ers Odds, Spread, and Total for Preseason Week 1

Odds via DraftKings Sportsbook

Spread

Titans -4.5 (-115)
49ers +4.5 (-105)

Moneyline

Titans -225
49ers +185

Total

OVER 39.5 (-125)
UNDER 39.5 (+105)

Titans vs. 49ers How to Watch NFL Preseason Week 1

Date: Thursday, August 13
Time: 9:00 p.m. ET
Venue: Levi's Stadium
How to Watch (TV): NFL Network
Titans record: 0-0
49ers record: 0-0

Titans vs. 49ers Preseason Betting Trends

Robert Saleh is 10-2-1 straight up and 10-3 against the spread as a head coach in the preseason
Kyle Shanahan is 14-12-1 straight up and 15-11-1 against the spread as a head coach in the preseason

Titans vs. 49ers Key Player to Watch

Cam Ward, QB - Tennessee Titans

Saleh has announced that all of his players will be on the field for at least a handful of plays on Thursday night, which means we'll see Cam Ward in his first game action of 2026. The 2025 No. 1 overall pick had a disappointing rookie campaign. He completed just 59.8% of passes for 3,159 yards, 15 touchdowns, and seven interceptions. The performance was somewhat forgivable having to play behind an offensive line that gave up 55 sacks and had few offensive weapons to lean on. He'll need to play much better in 2026, so we'll see if he can start to look like the player the Titans drafted when he takes the field against the 49ers.

Titans vs. 49ers Prediction and Best Bet

Saleh plans on playing all of his players for a portion of this game, while Kyle Shanahan has announced that he'll be resting his starters, which has led the Titans to be set as 4.5-point road favorites in this one.

I'm going to lay the 4.5-points with Tennessee, but it's not only because of their starters seeing the field. Betting on preseason football has a lot to do with how coaches treat the games. Most coaches will use them simply as an evaluation tool and don't care if it ends in a win or a loss, while others place importance on winning. Saleh, based on his small sample size as a head coach, belongs to the latter of the two groups. Despite coaching a bad Jets team, he had a 10-2-1 record and a 10-3 mark against the spread in exhibition games.

If that carries over to his tenure with the Titans, Tennessee is going to be a great preseason bet.

Pick: Titans -4.5 (-115) via DraftKings

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