Football is officially back with a loaded slate of preseason action across the Thursday night slate. With kickoff scheduled for 9:00 p.m. ET, the Tennessee Titans will face the San Francisco 49ers in their first action of the 2026 season.
Looking at the odds for the preseason matchup, the Titans enter as 4.5-point favorites and hold -218 odds of winning outright on DraftKings Sportsbook. The 49ers hold +180 odds of pulling off the upset, with the game total set at 39.5 points.
Titans at 49ers prediction, pick
Tennessee Titans preview
The Tennessee Titans will be looking to improve off of back-to-back 3-14 seasons as they enter this year. Robert Saleh has stepped in as head coach and will attempt to propel the team forward in Cam Ward’s second season at the quarterback spot. There were more encouraging flashes than the raw record indicates, but still plenty of work to do heading into the 2026 season. This preseason matchup will be the first look at the 2026 iteration of the Titans as the Saleh era kicks off.
Tennessee has committed to playing all of their starters, and could see more extended opportunities than is often the case in preseason. Saleh has refused to put a direct label on how long they will remain on the field, but has made it clear it will be more than just an opening drive. Ward started all three preseason games last year, but will need to take a step forward and settle in with his new teammates, headlined by rookie wide receiver Carnell Tate.
When Ward is removed from the game, there is a respectable level of talent in the quarterback room beyond the former first overall pick. Mitchell Trubisky is listed as second on the depth chart, while Will Levis joins him and also has experience as a starter. Hendon Hooker is the most inexperienced quarterback of the group, and has bounced around a bit since being selected with the 68th overall pick in the 2023 NFL draft by the Lions. But Hooker is a dual-threat quarterback who is capable of creating eye-popping plays and will be eager to show why he is deserving of a chance to climb the depth chart.
Beyond the quarterback position, there is plenty of competition across each of the members of the offensive line. While fourth overall pick Carnell Tate is expected to headline the wide receiver production, there is plenty of competition behind him. Elic Ayomanor is pushing Calvin Ridley for the starting role, while KJ Osborn, Xavier Restrepo, and Bryce Oliver have had some encouraging flashes in training camp. Each will be looking to make a strong impression in the opening preseason matchup to improve their standing in the organization.
San Francisco 49ers preview
The San Francisco 49ers finished last season with a 12-5 record, but were eliminated by the eventual Super Bowl Champion Seattle Seahawks in the postseason. It has been a bit of a rocky training camp for San Francisco already. Injuries have popped to the forefront of the conversation, including head coach Kyle Shanahan. He is back on the practice field following the serious car crash, but has missed some time. Beyond Shanahan, many of the starters are expected to be held out of this preseason opener. Injuries have been one of the biggest factors in this team getting over the championship hump, and they are looking to maximize their chances of having a healthy regular season. Christian McCaffrey has been held out of recent practices with tightness, while Nick Bosa has missed time with soreness on his surgically repaired knee.
It feels unlikely that Brock Purdy will see the field much, if at all, in this preseason opener. This will leave Mac Jones to take on the bulk of the quarterback responsibilities. He suited up for eight starts and made 11 appearances amid Purdy’s injury issues last year, and Jones has 57 career starts at the NFL level in his career. Kurtis Rourke and Adrian Martinez are also expected to see some level of opportunity.
If this roster can get fully healthy and play to their peak in the regular season, the 49ers have a deserving place in the contending conversation. But the clear calculation for the franchise is that the best path to accomplish this is by holding out as many key members as possible of these preseason matchups. Expect plenty of players battling for the final roster spots to dominate the snap counts in this matchup and for the primary focus of this 49ers’ team to be on evaluation.
Titans at 49ers best bet
This is a clear example of two organizations approaching this matchup with very different levels of intensity. The Tennessee Titans are intent on turning around their organization’s outlook, and this will especially be the case with it being the first opportunity for Robert Saleh to lead this group. It is just preseason, but there will be some added intensity given that Saleh served as the defensive coordinator for the 49ers last year, and coached in the organization for five seasons in total.
There will be a clear effort made to get Cam Ward on the right pathway to production and build his confidence on this stage. Turning the ball over to Trubisky, Levis, and Hooker is a higher floor of production than many preseason quarterback groups, especially given that many of the key defensive players on the 49ers roster will not be on the field.
From a side’s perspective, my lean is toward the under. The game total has gone over in seven consecutive preseason road games for the Titans. In addition, the game total was 9-5 to the over across the Jets’ preseason matchups when Saleh served as the head coach. With strong quarterback play across the board, expect points to come easy in this matchup.
But I am jumping all over the Titans on the -4.5-point spread as my best bet. Expect Saleh to fire up the squad as if this were a regular season game and for the Titans to lean on their superior talent level based on availability. Saleh has a 10-3 record against the spread in preseason as a head coach, and will be eager to take down the organization he most recently represented. Expect a bit of a statement from the Titans in this matchup and for Tennessee to pour on points at a rate the 49ers cannot match to comfortably cover the 4.5-point spread.
