Titans vs. 49ers Prediction: NFL Preseason Best Bets, Preview & Expert Picks (Aug. 13)

My best Titans vs. 49ers prediction for Thursday's 9 p.m. ET (NFL Network) game at Levi's Stadium in Santa Clara, Calif., focuses on the Titans playing most of their starters and the 49ers resting most of theirs. The opening odds showed the Titans as 2.5-point favorites, but early picks have favored the Titans, and they're now favored by 4.5 points.

Below, I explain why the Titans covering the spread is one of my best NFL Preseason Week 1 predictions.

🏈 Titans vs. 49ers early prediction: NFL Preseason

See the latest NFL odds and our experts' NFL picks for every game this season.

Titans -4.5 (-115) ⭐⭐⭐

The Titans are planning on playing all of their starters, while many key 49ers won't see the field on Thursday. This may not mean much, as Titans quarterback Cam Ward didn't throw more than eight passes in a preseason game last season. But with little else to go off of, this difference in approach is enough for me to back the Titans.

For what it's worth, Titans' head coach Robert Saleh is 10-2-1 in preseason games. In his last season as a head coach, he led the Jets to a 3-0 preseason record, something he accomplished twice with New York.

📊 Titans vs. 49ers odds: NFL Preseason

Titans vs. 49ers odds update live in real time. Our NFL analysis and expert predictions cover every game this preseason.

Titans vs. 49ers opening odds

• Moneyline: Titans -160 | 49ers +135
• Spread: Titans -2.5 (-110) | 49ers +2.5 (-110)
• Over/Under: Over 38 (-110) | Under 38 (-110)

Titans vs. 49ers line movement

Since the 49ers' head coach Kyle Shanahan announced that his starters won't be playing much, the public has been all over the Titans. The Titans, who will be starting Ward, are favored by 4.5, and some sportsbooks have already moved this line to 5.

I fully expect this number to continue to increase, though I'd be surprised if it got to 7 points. After all, the Titans are playing their starters, but this is a team that went just 3-14 last season. As for the total, there hasn't been much movement, and I don't expect that to change before kickoff.

📈 Titans vs. 49ers trends & betting notes: NFL Preseason

• Four consecutive 49ers' preseason games have featured at least 39 points. However, five of the Titans' last seven preseason games have featured 36 or fewer points.
• Cam Ward hasn't thrown a touchdown pass in any of his three preseason games.
• As a head coach, Saleh is 10-3 ATS in preseason games.

📺 How to watch Titans vs. 49ers: NFL Preseason

• Date: Thursday, Aug. 13, 2026
• Kickoff: 9 p.m. ET
• Location: Levi's Stadium (Santa Clara, Calif.)
• TV: NFL Network