49ers vs. Colts Predictions & Odds for Monday Night Football
The Philip Rivers experiment continues for a second straight week in this Monday Night Football matchup as I make my best 49ers vs. Colts predictions. Kickoff from Lucas Oil Stadium in Indianapolis is set for 8:15 p.m. ET (ESPN), with San Francisco currently listed as anywhere from 5.5 to 6-point betting favorites.
My NFL Week 16 predictions eschew the point spread and instead buy low on the Colts' offense, enough to cash the Over.
🏈 49ers vs. Colts prediction: Monday Night Football
Don't miss the rest of our NFL picks for every game this season.
Over 46.5 (-102) ⭐⭐⭐⭐
San Francisco has played some of its best offensive football during a four-game winning streak.
Since Week 11, when quarterback Brock Purdy returned from injury, the 49ers rank fourth in points per game (31.0), second in Total QBR, first in third-down rate, and sixth in Offensive Efficiency.
Indianapolis has averaged 17.8 points per game in that span while producing its four lowest yardage totals of the season. But opposing quarterbacks average more than 23 completions per game against San Francisco, so Rivers should fare better than he did in his NFL return last week.
DraftKings is the only one of our best sports betting sites with better than a -110 price (52.38% implied odds). Its -102 odds would net $9.80 in profit on a $10 wager if the Over cashes.
Score prediction: 49ers 27, Colts 24
💡 More Week 16 predictions
Want more NFL betting advice? Check out all of our NFL analysis and expert predictions for every game in Week 16.
🙌 Best 49ers vs. Colts TD pick
Search the best NFL player prop odds for any team or player across every market from legal sportsbooks in your area.
Christian McCaffrey, RB, 49ers: To score a first-half touchdown (+130) ⭐⭐⭐
Brock Purdy’s return from injury has opened up San Francisco’s running game, as defenses must honor his second-ranked Total QBR since Week 11.
In those four games, San Francisco has rushed for six touchdowns and averaged 117.8 yards per game on the ground. That is the same amount of rushing touchdowns the team had through the first 10 weeks, when it averaged 94.8 rushing yards per game.
Backing McCaffrey to score in the first half is a great way to mitigate his steep anytime touchdown odds that carry as high as a 69.23% implied probability based on a market-high -225 price.
Best prop bet: Christian McCaffrey to score a first-half touchdown (+130 via DraftKings)
📊 Live 49ers vs. Colts odds
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📈 49ers vs. Colts betting trends
| 49ers | Statistic | Colts |
|---|---|---|
| 10-4 | W-L record | 8-6 |
| 8-5-1 | ATS record | 9-5 |
| 8-5-1 | O/U record | 7-7 |
| 5.50 | Yards per play | 6.13 |
| 5.68 | Yards allowed per play | 5.45 |
| -5 | Turnover margin | +2 |
| 4-1 | Last 5 games | 1-4 |
| W, 37-24 vs. Titans | Previous result | L, 18-16 vs. Seahawks |
🚑 49ers vs. Colts injury report
🌤️ 49ers vs. Colts weather
This game will be played indoors at Lucas Oil Stadium, so weather won't be a factor for 49ers vs. Colts on Monday.
Check our NFL weather report for the latest forecasts and betting impacts for every game this week.
📺 How to watch Monday Night Football: 49ers vs. Colts
- Date: Monday, Dec. 22
- Kickoff: 8:15 p.m. ET
- Location: Lucas Oil Stadium (Indianapolis)
- TV: ESPN
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