HomeNFLNFL PredictionsTennessee Titans vs San Francisco 49ers Predictions, Odds & Expert Picks for NFL Week 15 2025

Tennessee Titans vs San Francisco 49ers Predictions, Odds & Expert Picks for NFL Week 15 2025 for Today, 12/14/25

Updated: 4:52 AM ET Dec 14, 2025

Levi's StadiumFOX

Titans

4:25 PM ETToday

49ers

LLLLW	Last 5	WLWWW
2-11	Record	9-4
6-7-0	ATS Record	8-5-0
8-5	O/U Record	7-6

Titans vs 49ers Pickswise Expert Predictions

Point Spread Pick

SF 49ers -12.5(-110)

Reasoning

The Tennessee Titans picked up their 2nd win of the season last week with a 31-29 victory over the Browns, but could be brought back down to earth when they head to Levi’s Stadium to battle the San Francisco 49ers. Despite all those points, quarterback Cam Ward continued to struggle as he completed just 50 percent of his passes for 117 yards, while it was running back Tony Pollard who did the heavy lifting. Ward has been kept under 200 passing yards in 4 of his last 5 games and has thrown just 9 touchdown passes in 13 games, and 49ers defensive coordinator Robert Saleh has to be salivating at letting his players loose on Ward.

But it’s the San Francisco offense that gives me confidence that they’ll be able to cover this lofty spread. The 49ers had their bye last week so will be raring to go in this one, and each of their last 5 victories have come by double digits. Christian McCaffrey has been in outrageous form even by his standards, and should dominate a Titans defense that has given up the 2nd-most rushing touchdowns along with the 2nd-most passing yards per attempt. With the San Fran attack getting healthy, we could see them run up the score here especially as they look to keep tight with the Rams and Seahawks, and it’s hard to see Tennessee having much of a response.

Titans vs 49ers prediction: 49ers -12.5 (-110) available at time of publishing. Playable to 13.

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Game Totals Pick

Over 44.5(-110)

Reasoning

With the offense getting healthy this 49ers team is really starting to click into gear, highlighted by them posting at least 26 points in 4 of their last 5 games, and we should see them run up the score against the Titans. Both Christian McCaffrey and George Kittle have been excellent for this offense, while Brock Purdy appears to be getting back into a groove. San Fran has the 7th-most passing yards per attempt and 7th-most passing touchdowns this season, and they should be able to carve up this vulnerable Titans defense.

While Cam Ward has been pretty anemic this season, he does get to go up against a 49ers D decimated by injuries, which has resulted in them allowing the 6th-most passing TDs themselves and generated the fewest sacks in the NFL. Tony Pollard exploded for 161 rushing yards and 2 touchdowns last week, and he could also give Saleh and this Niners defense some headaches. While San Francisco should do a lot of the heavy lifting in this one, I believe the Titans can contribute enough to the total to send this game Over.

Titans vs 49ers prediction: Over 44.5 (-110) available at time of publishing. Playable to 45.5.

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Managing Editor of Pickswise. Born and raised in jolly old London, England, with an undying love for the NFL, NBA, soccer and horse racing. A big-time sports bettor who loves futures markets and backing underdogs. Long-suffering New York Jets fan. For Andrew Wilsher media enquiries, please email contact@pickswise.com.

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Point Spread

The Titans have covered the spread in 4 of their last 5 games against teams with better records.

Money Line

The Titans have lost 4 of their last 5 games away to teams with winning records.

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