Indianapolis Colts vs San Francisco 49ers Preview & Props (10/22): Rock with Brock
Written by: Danny Burke
Last Update: Mon Dec 22, 2025, 1:28 pm ET
Read Time: 8 minutes
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A winner of four straight and a loser of four straight square off on Monday Night Football, as Philip Rivers makes his second consecutive start under center for the Colts, who host the 49ers at Lucas Oil Stadium in Indianapolis.
San Francisco clinched a playoff berth on Sunday night thanks to Aaron Rodgers and the Steelers eliminating the Detroit Lions from Wild Card contention. Still, the 49ers have plenty to play for, as they remain in the mix for overall seeding and the top spot in their division.
On the other side, the Colts need just about everything to break their way. According to the New York Times Playoff Simulator, Indianapolis enters the night with just a 3% chance of reaching the postseason.
Can the Colts defy those odds as 5.5-point home underdogs? I'll break it down below with my Colts vs. 49ers preview and picks.
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Indianapolis Colts vs San Francisco 49ers Preview & Props
Brock Purdy aims to lead San Francisco to a fifth consecutive victory on Monday Night Football in Indianapolis.
Colts vs 49ers Preview
Both of these teams enter this game with a laundry list of injuries.
San Francisco will be without wide receiver Ricky Pearsall, linebacker Nick Martin, and cornerback Renardo Green. Defensive end Yetur Gross-Matos, one of their key contributors up front, is also listed as questionable.
Indianapolis will be without cornerback Sauce Gardner, quarterback Anthony Richardson, offensive tackle Bernhard Raimann, and safety Daniel Scott. The good news is that the Colts also have a major question mark on the defensive line, with DeForest Buckner listed as questionable.
Despite the number of absences on both sides, the betting market has remained relatively steady throughout the week. The line opened with the 49ers laying 5.5 points and the total hovering around 46, and it has largely stayed there.
Already with their backs against the wall, what should we expect from this Colts defense against Brock Purdy and his supporting cast?
Through five starts this season, Purdy has completed 68% of his passes for 1,442 yards, though his 12-to-7 touchdown-to-interception ratio is slightly concerning.
He opened the year by leading the 49ers to a 17–3 win in Seattle, then missed the next two weeks before returning in Week 4 against Jacksonville, a 26–21 loss. Purdy would hit the injury report once again and wouldn't return until Week 11 at Arizona, where he guided San Francisco to a dominant 41–22 win. Since coming back in November, he's led the 49ers to a perfect 4–0 record.
But just how efficient has he really been? It's fair to note that those wins have come against the Cardinals, Panthers, Browns and Titans. Outside of Cleveland, those are among the league's weakest defenses.
Still, the underlying metrics paint a strong picture. Since Week 11, among 32 qualified quarterbacks, Purdy ranks first in CPOE, second in success rate and third in EPA per play. He's been far more efficient than public perception might suggest.
That efficiency could continue tonight, especially against a Colts secondary that's struggled all season. Indianapolis is allowing 10.4 yards per completion (23rd), ranks 21st in dropback success rate and 15th in dropback EPA.
If we isolate their four-game losing streak, those numbers dip further. During that stretch, the Colts rank 26th in dropback EPA and 24th in dropback success rate.
The one area where Indianapolis has held firm is up front, where they rank top-six against the run in both EPA and success rate. Even so, this matchup sets up favorably for Purdy and the 49ers' passing attack.
Conversely, it's hard to carry the same level of confidence with 44-year-old Philip Rivers. To his credit, what he accomplished in his first start post-retirement was beyond impressive. Keeping the Colts competitive on the road against Seattle – and giving them a chance to win – was remarkable. However, there's a strong possibility he falls back to reality.
This time around, 49ers defensive coordinator Robert Saleh will have a clearer blueprint for what Indianapolis looks like with Rivers under center. While everyone knew his physical limitations going in, having a full-game sample of the formations, tempo and concepts the Colts are willing to run makes a difference. That preparation edge should show up on Monday night.
Against Seattle last Sunday, Rivers completed 18 of 27 passes for just 120 yards – a mere 4.4 yards per completion – with one touchdown and an interception that ended the game. Shockingly, he was sacked only once against one of the league's better defenses.
Now he draws a San Francisco unit that's quietly trending upward. During their four-game win streak, the 49ers rank first in dropback success rate and fifth in dropback EPA. Their secondary has played significantly better football over that stretch, a stark contrast from their full-season rankings, where they sit 24th in both metrics.
Where San Francisco has consistently struggled, however, is against the run. They've ranked in the bottom half all season, and during this recent stretch they've fallen to dead last in rush success rate allowed and 23rd in rush EPA.
That opens the door for Jonathan Taylor to shoulder the load. If the Colts are going to pull off the upset, it may require Taylor putting the offense on his back and carrying them across the finish line.
Colts vs 49ers Props
From a prop perspective, the only area of interest for Indianapolis is the passing game via the running backs, with Ameer Abdullah standing out. Unfortunately, no sportsbook is currently offering prop markets for his receptions or receiving yards.
Last week, Abdullah caught all five of his targets for 32 yards. Given Rivers' limitations, an uptick in short dump-offs to the running backs is inevitable. Frankly, that should be a focal point regardless of who is under center.
San Francisco has been extremely vulnerable to running backs in the passing game this season, allowing nearly six receptions per game and more than 34 receiving yards per contest to the position.
Luckily, there are a pair of props on San Francisco's side that show value.
As noted earlier, Brock Purdy is set up for success in this matchup. Since returning to the lineup, he's been one of the most efficient quarterbacks in the league, ranking first in CPOE, second in success rate, and third in EPA per play during the 49ers' four-game win streak.
That efficiency lines up well against an Indianapolis secondary that's been the clear weak point of their defense all season and has continued to trend in the wrong direction. During the Colts' four-game losing streak, they rank 26th in dropback EPA and 24th in dropback success rate. Over their last three games, they've also surrendered 12.4 yards per completion, the second-highest mark in the league over that span.
Each of the last four quarterbacks to face this Indy secondary – Sam Darnold, Trevor Lawrence, C.J. Stroud and Patrick Mahomes – has cleared 240.5 passing yards.
Purdy should hold a clear edge through the air and may need to lean on it given how dominant the Colts have been against the run. All signs point to San Francisco emphasizing the passing game, putting Purdy in a strong position to deliver with his arm tonight.
Additionally, I'm backing San Francisco kicker Eddy Pineiro to go over 1.5 field goals. Pineiro has been perfect this season, converting all 25 of his field-goal attempts. He's made at least two field goals in nine of 11 games, with the only exceptions coming in games where he didn't attempt a kick at all.
Beyond his efficiency, the matchup itself creates solid kicking opportunities. The Colts boast a top-10 red-zone defense, allowing touchdowns on just 52.8% of opponent trips inside the 20. That number has improved even further over their last three games, dropping to 41.7%, which could force San Francisco to settle for field-goal attempts rather than touchdowns.
Bets:
NFL record: 90-75-1 (+6.15 units)
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Danny Burke is a betting analyst with a decade of sports media experience. He got his start at the University of Nebraska-Lincoln, sharing picks on the local ESPN affiliate. After college, he hosted shows for VSiN in Las Vegas before returning to Chicago to launch 'Rush Hour', the first daily sports betting show from an Illinois casino. He also co-hosted 'Props and Locks' on Fox32’s Bears pregame show and ran 'Bet On, Chicago' on WLS-AM 890.
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