Titans vs 49ers Best Bets, Odds & Who’s Playing?

The Tennessee Titans and the San Francisco 49ers will open their preseason action this Thursday, August 12, at Levi’s Stadium in Santa Clara, California, with kickoff set for 9 p.m. ET. 

I’ll break down this matchup from an analytical perspective while taking into account the numerous expected absences on both teams, as starters resting in the preseason is common in the NFL.

Titans vs 49ers Odds

Odds from Kalshi as of Thursday, August 13, 2026 at 4:30 p.m. ET

At first glance, it might be a surprise to see the Titans listed as the odds-on favorites ahead of this contest, especially if we consider the sizable gap between both teams when it comes to analyzing their odds to make the NFL Playoffs. 

However, the Titans’ edge in the ML lies in the fact that Tennessee will have several starters on the field for at least a few series, whereas it’s already known that the 49ers will hold out most of their starters here. It’s also not surprising to see the Titans getting the edge when it comes to our NFL public betting data. The public is clearly backing Tennessee to win.

Titans vs 49ers Picks and Best Bets

When it comes to the best bets for this 2026 NFL preseason matchup, these are my best bets and picks for Thursday’s contest at Levi’s Stadium.

Best Pick: 49ers +5.5 (48¢, Kalshi)

I acknowledge that the Titans are the favorites, but the 49ers have a deeper roster, which is why they have a higher win total than the Titans in the NFL win totals ahead of the 2026 regular season. San Francisco should be able to keep the game close once the backups are in. 

With that in mind, I’m backing the 49ers to cover the +5.5 spread, meaning they’re either likely to win the game or lose by no more than five points. If the starters on both teams were playing, there’s no doubt the 49ers would be favorites ATS and on the ML, but having backups certainly limits the scope of the analysis.

Best Over/Under Pick: Under 40.5 total points (52¢, Kalshi)

Preseason games tend to be sloppy, and defenses often get the best of offenses, as this is the first time many backups are playing together — and in some cases, this is the first taste of “competitive” football since late December or early January.

If we add into the mix the fact that both teams will either limit their starters (Titans) or rest them altogether (49ers), it’s hard to imagine a scenario in which the over hits the mark. With backups, rookies and players fighting for their jobs on offense series after series, it’s difficult to see this game featuring too many points.

Titans vs 49ers: How to Watch, Kickoff Time and Streaming

Titans vs 49ers: Injury Report and Expected Absences

As it’s often the case in preseason, both teams will be resting several key starters with the start of the 2026 regular season right around the corner. Let’s take a look at the injury situation and rotation opportunities for both teams.

Titans Projected Absences in 2026 NFL Preseason Week 1

When it comes to the Titans, Terry McCormick of TitanInsider.com indicated that Ward is one of several starters expected to see action in the preseason opener. Don’t expect the sophomore signal-caller to play the entire game, though. As it’s often the case when the starters suit up for a preseason game, the second-year signal-caller could be in line for a couple of offensive series at most before making way for the backups. Once Ward is no longer on the field, look for Mitchell Trubisky and Will Levis to battle in their tight quest to see who wins the backup role.

The Titans are mostly healthy ahead of this preseason opener, with their lone injury concerns being safety Sanoussi Kane (undisclosed) and running backs Kalel Mullings (hip) and Tyjae Spears (undisclosed). Kane is on injured reserve and will miss the entire 2027 season, while Spears and Mullings will miss out on the chance to see extra work after the starters come off the field at some point in the first half.

49ers Projected Absences in 2026 NFL Preseason Week 1

When it comes to San Francisco, Brock Purdy won’t be playing, and the same goes for several key starters on both sides of the ball. Christian McCaffrey (undisclosed), Mike Evans (quadriceps), George Kittle (Achilles) and Nick Bosa (right knee tendonitis) are among the players who won’t be suiting up Thursday, creating playing time opportunities for several backups. 

Mac Jones is firmly entrenched as the 49ers’ QB2 entering the season, so it wouldn’t be a surprise if Kurtis Rourke and Adrian Martinez end up seeing most of the snaps on Thursday. Demarcus Robinson, De’Zhaun Stribling, Luke Farrell, Jordan Watkins and Patrick Taylor are some of the names who could be in line for additional work in this preseason opener as well.