49ers vs. Titans Point Spread: NFL Week 16 Odds, Prediction

Payton Matthews | Updated Dec 21, 2021

It’s the final Thursday night game of the NFL season in Week 16 as the Tennessee Titans host the San Francisco 49ers.

December 23, 2021, 8:22 PM ET
Nissan Stadium
Pointspread -3.5 -105
Moneyline -190
Over / Under o +45.5


Betting Action


Pointspread +3.5 -115
Moneyline +158
Over / Under u +45.5


Betting Action


San Francisco is a 3.5-point favourite to win on the NFL odds with a total of 44.5 points.

NFL Point Spread and Betting Analysis

While the NFL regular season is now 17 games instead of 16 and thus 18 weeks instead of 17, the league doesn’t want to disadvantage any teams in the final two weeks in regards to a very quick turnaround Thursday game, so this is it for the 2021 season.

Both the 49ers and Titans should be playoff teams – Tennessee is going to win the AFC South. The Titans remain without superstar running back Derrick Henry due to a foot injury suffered on Halloween, but there’s hope he can return for the regular-season finale if that matters or the playoffs if that regular-season finale is meaningless. San Francisco will have to get in the NFC post-season via the wild-card route. Good news: The Niners have a sure win Week 17 vs. Houston. Bad news: They finish with a very tough game at the Rams.

Since the Titans moved from Houston to Nashville, the 49ers lead the series 3-2 and have won the previous two. They last met in 2017 in the Bay Area and San Francisco prevailed 25-23 on a 45-yard field goal as time expired by Robbie Gould. He’s still with the team and hit six field goals that day.

San Francisco 49ers

San Francisco (8-6) currently holds the second wild-card spot in the NFC as the No. 6 seed. The Niners won for the fifth time in six games Sunday, 31-13 over the visiting Atlanta Falcons. Since Week 8, Jimmy Garoppolo has been one of the league’s most efficient quarterbacks and he was excellent in the win, completing 18 of 23 passes for 235 yards and a score. Rookie and top running back Elijah Mitchell missed the game with a concussion and knee injury and could be a game-time call Thursday. Jeff Wilson took over as the featured back and rushed 21 times for 110 yards and a score. Linebacker Azeez Al-Shaair missed it with an elbow injury and could also be game-time call Thursday. He’s having a breakout season with 96 tackles, two fumble recoveries and 1.5 sacks. The 49ers are 5-1 ATS in their past six games.

Tennessee Titans

The Titans’ lead atop the AFC South over Indianapolis is down to a game but Tennessee wins the head-to-head tiebreaker. It was beaten Sunday in Pittsburgh, 19-13. Pro Bowl receiver AJ Brown was out again with a chest injury but has been designated to return from injured reserve. Fellow Pro Bowl wideout Julio Jones hasn’t been able to stay healthy much this year, either, and he left Sunday’s game with a hamstring injury. Seems unlikely that he’ll play Thursday. The Titans and quarterback Ryan Tannehill have turned the ball over 13 times in the last four games, and they are averaging just 14.8 points in that span. Tannehill has two TDs and six picks in them. Tennessee is 1-4 ATS in the past five.

NFL Prediction: Who Will Win 49ers vs. Titans?