San Francisco 49ers vs Indianapolis Colts Public-Betting Splits & Injury Reports

• A cross-conference matchup ends Week 16
• The public expects the 49ers to win big
• Keep reading for the 49ers vs Colts public-betting splits and final injury reports

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The final game of Week 16, the San Francisco 49ers (10-4) head east to face the Indianapolis Colts (8-6) on Monday Night Football. The 49ers are locked into a playoff spot while three AFC teams could clinch a postseason berth if the Colts lose. ESPN and ABC will simultaneously broadcast the 8:15 pm ET kickoff from Lucas Oil Stadium on Dec. 22.

The 49ers are road favorites in the MNF odds. The public is leaning toward the over tonight.

49ers vs Colts Public Betting Splits

As of Monday afternoon, the public is backing the road favorites, the 49ers, in the NFL public betting percentages. San Francisco is getting 66% of the ATS handle with 65% of bets coming in on the playoff-bound squad. The Colts are only getting 34% of the ATS handle with 35% of bets.

Bettors are hammering the 49ers moneyline for MNF. A whopping 81% of the handle is on the 49ers to win, with an overwhelming 87% of all bets coming in on the favorites. For the underdog Colts, only 19% of the handle is backing them to win. Only 13% of all moneyline bets are on the Colts.

The public is solidly on the over for MNF. For the total, 74% of the handle is on the over with a healthy 61% of all bets placed. Meanwhile, the under represents just 26% of the handle and 39% of bets. Fellow writer Chris Amberley is fading the public, taking Under 46.5 in his 49ers vs Colts picks and predictions.

Looking for 49ers vs Colts picks to tail? Check out …

• Sascha Paruk’s +347 49ers vs Colts Same-Game Parlay
• John Hyslop’s pair of plus-money SF 49ers vs IND Colts Player Props to Target
• Ryan Potts’ top MNF Anytime Touchdown Picks

SF 49ers vs IND Colts Injury Reports

The 49ers have ruled three players out for MNF. Additionally, edge defender Yetur Gross-Matos is questionable with a hamstring injury. The six-year vet has not played since October 2. He would be a boon to a pass rush that ranks last in the NFL in sacks. Gross-Matos has 17.0 sacks in his NFL career, recording 4.0 last season.

Renardo Green will be heavily missed. The second-year cornerback had played 91% of San Francisco’s defensive snaps through 13 games. He has nine pass deflections and 52 total tackles. He has a 56.2 PFF Coverage grade in 470 coverage snaps. Without Green, watch for Darrell Luter and Siran Neal to play more snaps.

Renardo Green is lockdown! 🔒💯🔥

pic.twitter.com/qdirBySrls

— TJ Salomone (@TJSalomone) November 25, 2025

Another second-year player, Pearsall, has continued to deal with injuries in his NFL career. He has played eight games this season, catching 31 passes for 443 yards. Last week, he had six catches for 96 yards against the Titans. Without Pearsall, the 49ers will target the likes of Demarcus Robinson and Kendrick Bourne more in the offense.

The Colts have ruled out five players for MNF. Stud interior defender DeForest Buckner has been designated for return, but he is questionable for a revenge game against the 49ers. Buckner spent the first four seasons of his career in San Francisco before being traded to Indianapolis in 2020. Despite missing four games, Buckner has 4.0 sacks and nine tackles for loss this year.

Sauce Gardner will miss another game, his third in a row. The former All-Pro cornerback has only played three games with the Colts since Indianapolis sent two first-round picks (and Adonai Mitchell) to the Jets in exchange for his services.

Left tackle Bernhard Raimann will miss his first game of the season. The stalwart has played 97% of the Colts’ offensive snaps this season. He had been particularly sharp in the last five games, allowing just one hit and zero sacks.

Bernhard Raimann has returned to #Colts practice wearing a substantial brace over his right elbow. pic.twitter.com/Iik3PbA8F0

— Brett Bensley (@brettbensley) December 20, 2025

Both Anthony Richardson and Daniel Scott are currently on injured reserve, but they are designated for return. Richardson has thrown two passes this season. Scott played the first four games of the season as a key special teamer.