The San Francisco 49ers (10-4) and Indianapolis Colts (8-6) close NFL Week 16 on Monday Night Football on December 22. Kickoff is set for 8:15 p.m. ET from Lucas Oil Stadium in Indianapolis, Ind. The game will broadcast live on ESPN and ABC.
The 49ers are favored by -5.5 with the over/under set at 46.5 total points. San Francisco is a -250 favorite to win outright, while Indianapolis is +205 to pull off the upset.
Let's get into my Monday Night Football preview and 49ers vs Colts prediction.
49ers vs Colts Prediction
- 49ers vs Colts pick: Colts +5.5 (-112 | Play to +4)
My 49ers vs Colts best bet is on Indy to cover the spread. Find the best odds by checking our live NFL odds page.
49ers vs Colts Odds
| 49ers Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-5.5 -108 | 46.5 100o / -120u | -250 |
| Colts Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+5.5 -112 | 46.5 100o / -120u | +205 |
49ers vs Colts Monday Night Football Preview
Note: All data is via FTN unless otherwise noted.
Philip Rivers' first start since the 2020 season came last week against a Seahawks defense that currently ranks No. 1 in defensive DVOA, No. 2 in pass-defense DVOA, and No. 2 in pressure rate (35.1%).
Given that context, it's surprising that Colts head coach Shane Steichen was willing to start the 45-year-old Rivers fresh off the couch, and even more surprising that Rivers led the Colts to four scoring drives — including the game's only touchdown — in a narrow 18-16 loss.
The Colts offense is in a better spot against a 49ers defense that ranks No. 25 in overall defensive DVOA and pass-defense DVOA, and 31st in pressure rate (22.1%).
Rivers was pressured on only 6-of-27 (21.4%) of dropbacks last week, but that came by way of getting the ball out quickly, with a third of his attempts being targeted at receivers behind the line of scrimmage, leading to a ghastly 4.4 YPA average for the game.
The condensed passing offense allowed the Seahawks to key in on the run game, leading to decreased efficiency for Jonathan Taylor, who produced just 87 yards on 25 carries (3.5 YPC).
With more time to throw against a defense that allowed the lowly Titans to post a season-high in offensive EPA (13.17, per Pro Football Reference), the Colts should be able to improve on last week's showing, at the very least.
The Colts defense ranks 11th in DVOA and was the primary reason they were able to stay in the game last week, holding the Seahawks to 2-of-13 on third down and 0-of-2 in the red zone.
The Colts will again have to hold a top-10 NFC West offense in check, but several factors are working in their favor.
- The Colts rank No. 4 with a -13.33 defensive EPA mark vs. '21' personnel (2 running backs, 1 tight end), which the 49ers use on 22.6 plays per game — by far the highest rate in the NFL, according to SumerSports.
- The Colts are allowing just 17.2 points per game at home, fifth-best in the NFL, and 7.8 fewer points than they allow on the road.
- Defensive tackle DeForest Buckner (neck) is expected to return after a five-game absence. Despite appearing in only nine games, Buckner is second on the Colts in total pressures (33, per PFF). PFF grades him as the 11th-best interior lineman among 127 qualifiers this season.
- The impact of being without perimeter cornerbacks Charvarius Ward (IR-concussion) and Sauce Gardner (calf) is lessened by the 49ers losing No. 2 wide receiver Ricky Pearsall (knee), who is coming off a 6-catch, 96-yard performance and is responsible for half of the team's 100-plus-yard receiving games.
49ers vs Colts Prediction, Betting Analysis
Per our Action Labs data, underdogs since 2006 that open +2 to +7 in Week 16 are 114-74-4 (61%) against the spread (ATS) with an 18% ROI. The 49ers under Kyle Shanahan are 21-26 (45%) ATS as favorites of more than 5 points with a -14% ROI.
Although 6 is a key number in NFL betting, it's generally a good sign for the 'dog when the number ticks down inside of 6. This season, 'dogs +4 to +5.5 are 23-9 (72%) ATS with a 38% ROI.
Pick: Colts +5.5 (-112, DraftKings | Play to +4)
Parlay Pieces
- Jauan Jennings anytime TD +150: Jennings has scored in five of his last six games. He has scored on 12.1% of his targets from Brock Purdy this season compared to 7.3% from Mac Jones. The Colts will be without Ward and Gardner, who combined to not allow a touchdown on 383 snaps in coverage.
- Tyler Warren anytime TD +245: The 49ers are allowing 0.64 touchdowns per game to tight ends, tied for third-most. Warren posted a season-high 96.4% route participation rate last week.
- Jennings TD + Warren TD + Colts Spread +5.5
Parlay Odds: +1400 (DraftKings)
Spread
As mentioned, I'm backing the Colts to cover the spread.
Moneyline
I lean Colts for the moneyline.
Per our Action Labs data, moneyline 'dogs since 2003 facing an opponent on 8-10 days of rest in the 14th or 15th game of the season have won outright 40% of the time, producing a 45% ROI.
Over/Under
I lean under with the Colts, who are unlikely to produce many explosive plays on offense. They are also holding opponents to under 18 points per game at home on defense.
