49ers vs. Colts betting preview: Odds, picks, props, trends, injuries, weather and more for Week 16 Monday Night Football

In Week 15, we saw likely the last Monday Night Football game in the career of quarterback and future Hall of Famer Aaron Rodgers. It's more of the same tonight regarding 44-year-old Philip Rivers as his Indianapolis Colts (8-6) look to keep their slim playoff hopes alive when hosting the San Francisco 49ers (10-4), who have punched their ticket to the postseason. The Niners are -5.5 with a total of 46 for the 8:15 kick this week on both ABC and ESPN.

Both these teams entered Week 16 tied for the hardest remaining schedule in the NFL, as their opponents had a combined winning percentage of the same .690. We will start with San Francisco, which reached  three straight NFC title games from 2021-23 but imploded last year in part due to injuries and missed the playoffs. The Niners clinched at least a wild card spot on Sunday when Detroit was stunned at home by Pittsburgh.

The SportsLine Projection Model forecasts San Francisco to finish with the third-most wins in the NFC at 11.6 -- the team's preseason win total was 10.5 but the updated number is now 11.5 with the Over at -145. The Niners close with back-to-back at home against Chicago and Seattle, which might be locked into its seeding and rest guys. San Francisco still has a shot at the NFC West title and conference's top seed, thanks to the Seahawks' win on Thursday over the Rams, but they must win out. For the division, the 49ers are +370 and for the top seed +425.

It was all going so well for Indianapolis when it sat at 8-2, with quarterback Daniel Jones an MVP candidate and tailback Jonathan Taylor as the Offensive Player of the Year favorite. But Jones was of course lost for the season in Week 14, which partly necessitated the team's stunning signing of Rivers off his couch having not played in the NFL since 2020. And he'll start again tonight. The last team to miss the playoffs after starting 8-2 or better was the 1995 Raiders, who lost their final six. 

It's a little complicated now about the Colts reaching the postseason for the first time since 2020, but basically they have to focus on the Jaguars, Chargers and Texans and win out. That none of them lost on Sunday basically crushed Indy. The model gave the team just a 13.7% playoff shot before Sunday, and that is now 4.1%. It rises to 12.7% with a win but falls to 8.2% with a loss. DraftKings prices the team at  +1700 (was +700 before Sunday) with No at -8000.

We'll take you through every aspect of the 49ers vs. Colts game that you need to know before you lock in your bets, including SportsLine expert picks, props, trends, DFS, injury information and everything else that will help you know which plays are worth making for the primetime matchup.

Who wins 49ers vs. Colts in the Week 16 Monday night game, and what critical X-factor makes one side of the spread hit HARD? Join SportsLine right now to see everything you need to know to dominate your Monday Night Football bets, plus get expert picks, model sims, prop bets, DFS lineups, and more!