Tennessee Titans vs. San Francisco 49ers, Odds, Picks and Prediction for Sunday, December 14, 2025
Use Code WWWC Tennessee Titans (2-11) vs. San Francisco 49ers (9-4)
Week 15 of the 2025 NFL season is upon us, and in this preview, we are breaking down Sunday’s cross-conference showdown from Levi’s Stadium in Santa Clara, CA, to get you the Titans vs. 49ers prediction.
Tennessee meets San Francisco for the first time since 2021, when the Titans outlasted the 49ers 20-17 as 3.5-point home underdogs. The Titans are 12.5-point road dogs this time around, while the total sits at 44.5 points.
Read more about this Titans vs. 49ers prediction, and check out all our NFL picks for Week 15. The kick-off at Levi’s Stadium is set at 4:25 PM ET.
The Titans broke out of their funk in Week 14
The Tennessee Titans (2-11; 6-7 ATS; 8-5 O/U) put an end to their seven-game losing streak last Sunday. They beat the Cleveland Browns 31-29 as 3.5-point road underdogs, and Tony Pollard led the way with 25 carries for 161 yards and two touchdowns.
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Cleveland outgained Tennessee 412-292 in total yards, but the Titans won the turnover battle 2-1. Tennessee nearly blew a 31-17 lead. The Browns scored a couple of touchdowns down the stretch, but they missed both of their two-point conversions.
Rookie QB Cam Ward, the top overall pick in the 2025 NFL Draft, went 14-of-28 for 117 yards, two touchdowns, and an interception. It was his first game with multiple TD passes, which tells you a lot about the Titans’ offense.
“About time, honestly,” Ward said. “We have to continue to be efficient. I have to be efficient, throwing to my guys open, putting it in their radius to make plays.”
Ward has thrown for 2,468 yards, nine touchdowns, and seven interceptions this season. Pollard has rushed for 743 yards and four touchdowns, while rookie WR Elic Ayomanor has amassed 30 receptions, 353 yards, and three touchdowns.
The Titans score just 15.5 points per game (31st in the NFL) and allow 27.5 points in return (29th). Their defense is 18th in the league in rushing yards (122.5 per game), 23rd in passing yards (228.5), and 16th in 3rd down conversion (38.8%).
Key Injuries for Titans:
- CB Jalyn Armour-Davis (Achilles) is out.
- OG Kevin Zeitler is questionable.
The 49ers aim for their fourth straight W
The San Francisco 49ers (9-4; 8-5 ATS; 7-6 O/U) are coming off a bye. The Niners will try to extend their winning streak to four games when the Titans come to town. In their previous three outings, the 49ers have beaten the Arizona Cardinals 41-22, the Carolina Panthers 20-9, and the Cleveland Browns 26-8.
Two weeks ago, the Niners cruised past the Browns, covering a 5.5-point spread on the road. Cleveland barely outgained San Francisco 253-252 in total yards, but the 49ers won the turnover battle 2-0. San Francisco went 11-for-17 on 3rd down and held the Browns scoreless in the second half.
Brock Purdy made his third straight start in Week 13, throwing for 168 yards and a touchdown. He also scored once on his own. Christian McCaffrey rushed 20 times for 53 yards and a touchdown, while Jauan Jennings had four receptions for 67 yards and a TD.
"I love where we’re at right now. It’s been a long wait for a bye week. It’s finally here. Mentally and physically, it’ll be awesome to rest and be able to come back from that with four games to play for a chance to get in the playoffs is everything we could’ve asked for," 49ers head coach Kyle Shanahan said.
Purdy has struggled with injuries a lot this season. Across five starts, Purdy has tossed for 1,147 yards, nine touchdowns, and seven interceptions. McCaffrey has been outstanding thus far, mustering 1,655 yards from scrimmage and 13 touchdowns, while Jennings has amassed 458 receiving yards and five scores.
The Niners score 23.6 points per game (16th in the NFL) and surrender 20.7 points in return (8th). Their defense ranks 12th in the league in rushing yards (103.8 per game), 25th in passing yards (232.0), and 14th in 3rd down conversion (38.5%).
Key Injuries for 49ers:
- RB Christian McCaffrey (illness) is questionable but practiced on Friday.
- FB Kyle Juszczyk (ribs) is questionable.
- DT Sam Okauyinonu (ankle) is questionable.
Titans vs. 49ers Pick
Spread Pick for Titans vs. 49ers
- San Francisco 49ers -12.5 (5 units)
The 49ers overcame numerous injuries in 2025. They lost both LB Fred Warner and DE Nick Bosa for the season, and the 49ers’ defense still looks good. WR Brandon Aiyuk is probably done for the season, too, while FB Kyle Juszczyk is questionable for the upcoming clash against Tennessee.
The Niners have won five of their previous seven games overall, and each of those five wins has come by 10 or more points. Their offense is full of dangerous weapons, so I expect the Niners to torture the Titans’ defense.
Tennessee ranks 26th in the league in opposing red-zone percentage (63.0%) and 30th in opposing passer rating (103.7). The Titans’ defense leaves a lot to be desired, and their offense cannot be trusted despite that 31-point outburst against Cleveland, so I will lay 12.5 points with the 49ers.
Over/Under Pick for Titans vs. 49ers
- Over 44.5 (5 units)
Three weeks ago, Tennessee fought bravely against Seattle, losing 30-24 at home. Two weeks ago, the Titans laid an egg, suffering a 25-3 home defeat against Jacksonville. And then, the Titans managed to score 31 points against the Browns, whose defense has been solid for most of the season.
That’s why I said it is hard to trust the Titans’ offense. I can only hope they will be able to help the over backers in Week 15. The 49ers’ pass rush isn’t great by any stretch of the imagination. San Francisco is dead last in the NFL in sacks (16) and ranks 27th in opposing passer rating (101.1).
Hereof, I will take the over. I rely on the Niners’ offense to make a difference. The Titans won’t be able to cope with Christian McCaffrey, and the Niners will move the chains with ease.
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