49ers vs. Colts Expert Picks for Monday Night Football | MNF Predictions, Best Bets & Odds

With the NFC's top seed in their sights, the San Francisco 49ers (10-4) look to keep rolling tonight as road favorites against the desperate host Indianapolis Colts (8-6) on Monday Night Football (8:15 p.m. ET, ESPN). Our 49ers vs. Colts expert picks break down all of our MNF predictions and best bets with the 49ers favored by 4.5 points at Lucas Oil Stadium in Indianapolis as part of our NFL Week 16 predictions.

🏈 49ers vs. Colts expert picks: MNF predictions & best bets

All bets listed from our NFL experts with four-star confidence or higher. See all of our NFL picks and expert NFL analysis for Monday Night Football and more.

🔮 49ers vs. Colts prediction

Over 46.5 (-102) ⭐⭐⭐⭐

Mike Spector: "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. They've been excellent on the road ATS this season, easily putting up points on their way to a 6-2 ATS record away from home."

See Spector's full analysis in his 49ers vs. Colts predictions, including his favorite player prop bet and the best MNF betting trends, injury report, and more.

🔥 Best 49ers vs. Colts player prop pick

George Kittle Over 66.5 receiving yards (-114) ⭐⭐⭐⭐⭐

Phil Wood: "George Kittle has at least 67 receiving yards in five consecutive games. The Colts are allowing the second-most passing yards per game, and they’re allowing 66.3 yards per game to tight ends, which is the fifth-most in the league. Kittle also has at least four receptions in all but one game this season, and he’s been targeted at least nine times in three of his last five games."

See Wood's full analysis in his 49ers vs. Colts player props, including his best bet for Philip Rivers and Michael Pittman Jr. tonight on Monday Night Football.

⛏️ Best Brock Purdy player prop pick

Brock Purdy Over 243.5 passing yards (-112) ⭐⭐⭐⭐⭐

Dustin Saracini: "The Indianapolis Colts are just getting gashed through the air, coughing up 247 passing yards per game - good for 30th in football. Sam Darnold dropped 271 last week on the Colts' secondary, Trevor Lawrence went for 244 before him, and a struggling C.J. Stroud dropped 276 three weeks ago. I have all the faith in the world in this offense to light this Colts team on fire in what could end up being a blowout when the dust has settled."

See Saracini's full analysis in his Brock Purdy player props, including two more Over bets for the 49ers quarterback against the Colts on Monday Night Football.

🐴 Best Jonathan Taylor player prop pick

Jonathan Taylor Over 95.5 rushing yards (-115) ⭐⭐⭐⭐⭐

Saracini: "One thing is for certain: this Colts offense runs through Taylor, and will continue to as long as Philip Rivers is at the helm. Last week, in the quarterback's first start, JT carried the ball 25 times in an effort to limit Rivers' impact on the game. While he does have another week under his belt at the NFL level, I still see Taylor getting anywhere between 18 to 25 carries tonight. With that type of volume, I fully expect Taylor to be able to go over this number against a defense that's still without Fred Warner. "

See Saracini's full analysis in his Jonathan Taylor player props, including two more four-star plays for the Colts star running back against the 49ers tonight.

👴 Best Philip Rivers player prop pick

Philip Rivers Under 27.5 yards longest completion (-110) ⭐⭐⭐⭐⭐

C Jackson Cowart: "This was my favorite bet on Rivers last week, and it was never in doubt with his longest completion topping out at 17 yards. It was one of just four completions exceeding 10 yards, and it sure felt that way watching it live. The 49ers' pass defense isn't as stout as the Seahawks' historic unit - more on that later - but Rivers simply doesn't have the arm strength to push the ball downfield, and the Colts have clearly tailored their game plan accordingly with a heavy diet of short passes and Jonathan Taylor runs. Let's take advantage before the market overcorrects."

See my full analysis in my Philip Rivers player props, including my favorite Over bet for the Colts' 44-year-old quarterback tonight in his second start in five years.

🙌 Best 49ers vs. Colts anytime touchdown scorer pick

Jauan Jennings, WR, 49ers (+145) ⭐⭐⭐⭐⭐

Esten McLaren: "Jauan Jennings has led 49ers receivers in snap share in eight straight games. He's scored six touchdowns across his last six games, including two last week. He also leads the team's receivers with six red-zone touchdowns, eight receptions, and 16 targets inside the 20. The Colts will again be without cornerback Sauce Gardner tonight. Though he likely would've focused on Ricky Pearsall, that absence shifts around the entire defense and leaves Jennings with even more room to operate."

See McLaren's full analysis in his anytime touchdown scorer predictions for Monday Night Football, including a long shot at +800 odds for a defense to score tonight. You can follow all of our NFL touchdown props for the biggest games every week.

1️⃣ Best 49ers vs. Colts first touchdown scorer pick

George Kittle, TE, 49ers (+700) ⭐⭐⭐⭐

Sean Tomlinson: "George Kittle is producing one of his finest seasons, especially scoring-wise after reaching pay dirt six times across just nine games. He's been a target behemoth lately while logging nine-plus looks in two of his past three outings, a stretch that includes his season-high 88 yards last week. And now a rising football magnet gets to face a Colts defense that's given up the eighth-most yards to tight ends, and the unit is tied for the 10th-most receptions."

See Tomlinson's full analysis in his first touchdown scorer predictions for Monday Night Football, including a long shot at +2700 odds to score the first touchdown.

🚀 49ers vs. Colts same-game parlay

Here's a look at what our NFL expert Brenden Schaeffer is betting tonight with his best Monday Night Football SGP paying out at +675 odds:

See Schaeffer's full analysis in his 49ers vs. Colts same-game parlay, including his analysis for all three SGP bets for Monday Night Football. You can follow all of our NFL same-game parlay bets for the biggest games every week.

📊 49ers vs. Colts odds: MNF

See the latest NFL odds for every game in real time.

📺 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