Expert prediction
NFL Week 16: San Francisco 49ers vs. Indianapolis Colts Preview, Odds, Picks (Dec 22)
Pick rationale
Analysis & key factors
- 49ers vs. Colts total is 46.5 points.
- Philip Rivers again starts for the Colts.
- San Francisco 49ers are 5-1 ATS in the last 6 games.
Both teams have to win, as they find themselves in a very tough playoff race. The Colts are in trouble, having lost 4 in a row, while the Niners come to town with the same number of consecutive wins.
If you want more NFL odds and predictions, please follow this link.
How to Watch
- When: Monday, December 22, 8:15 pm ET
- Where: Lucas Oil Field, Indianapolis, Indiana
- How to Watch: ESPN
49ers vs. Colts Odds
Game Preview
With 4 wins in a row, the Niners are still in contention for the NFC West title and the NFC No.1 seed. Their schedule was a bit more favorable, with Shanahan’s boys facing teams like the Cardinals, Panthers, Browns, and the Titans.
They won all the matches without any problems, practically in routine fashion, and the fact that they are 5-1 ATS during those 6 matches speaks for itself.
As for the Colts, Philip Rivers started in Seattle, and the Colts almost won. It was 18-16 for the Seahawks, who won on a late field goal and failed to score a single touchdown. Nevertheless, this was the Colts’ 4th straight loss.
Rivers had 120 passing yards, one touchdown, and one intercepted pass. Though what was the problem here was the run game, which accumulated only 102 yards on the ground, Jonathan Taylor had 87 on 25 carries.
49ers vs. Colts Head to Head
In 46 matches, the Colts had 27 wins and the Niners 19. Indianapolis won the last 5 games.
49ers vs. Colts Predictions
San Francisco is a better team now, in better shape with more offensive solutions, and that’s why they’re going to win in Indianapolis. Furthermore, we take them to cover a 6-point spread.
- Free NFL Picks: 49ers -6
NFL
More Predictions
NFL Week 9 Upsets: Commanders Nasty Underdogs, Cardinals and Raiders Defending the Spread
Week 9 of the 2026 NFL season features several situational spots where short underdogs hold tactical, scheduling, or matchup advantages. There aren’t as many choices as in previous rounds, but there’s still enough for us bettors to make some money. Here is one straight-up upset pick and two point-spread underdog picks, backed by key tactical […]
NFL Week 9 Player Props: Pitts to Score a TD, Flournoy Continues to Grow
NFL Week 9 player props are here. We’ve waited to see the situation regarding potential absences and injuries, and with game day just around the corner, it was time to unleash the best player prop picks for this round. We have three selections for our bettors, carefully picked and evaluated following a thorough process. After […]
Broncos vs. Panthers Week 9 Picks: Young’s Poor Protection Will Cost Carolina
Best bet: Broncos ATS pick: Broncos -2.5 Bet Broncos vs. Panthers at BetUS Denver Broncos (6-2) hit the road to face the Carolina Panthers (3-4) and continue their excellent run. The Panthers have been on the downhill lately and are under pressure to win this game and get back to the winning side. Stay with […]
Giants vs. Eagles Week 9 Picks: Rested Giants After a Win in Philly
Best bet: Giants ATS pick: Giants -3.5 Bet Giants vs. Eagles at BetUS NFC East is completely wild these days. The New York Giants (4-2-1) lead the group, while the Philadelphia Eagles (2-6) sit last. The home team is in huge trouble, having multiple stars out due to injuries. The Giants also have some absences, […]
Browns vs. Saints Week 9 Picks: Indoor Arena Will Create Problems for Cleveland
Best bet: Saints -1.5 Straight up pick: Saints moneyline Bet Cardinals vs Cowboys at BetUS Cleveland Browns (5-3) are still in the mix for the playoffs. However, they will need to win in New Orleans against the Saints (2-5). Browns are very light underdogs here, sitting at +100 before we started writing this article. We […]