The San Francisco 49ers (10-4) travel to face the Indianapolis Colts (8-6) in a crucial Monday Night Football matchup with playoff implications for both teams, as the 49ers aim to solidify their NFC West standing and the Colts fight for an AFC wild-card spot.
Venue Location
Lucas Oil Stadium, Indianapolis, Indiana. This is a domed stadium with a retractable roof, typically closed for December games.
ESPN: Joe Buck, Troy Aikman, Lisa Salters (field reporter), Laura Rutledge (field reporter)
Westwood One: Kevin Harlan, Ross Tucker
Kickoff:
8:15 p.m. ET. The game will be broadcast on ESPN.
Injury Report
Both teams are dealing with key absences that could influence strategies, particularly on the lines and in the passing game.
San Francisco 49ers:
WR Ricky Pearsall: Out (ankle sprain and aggravated PCL sprain) – Significant loss for the receiving corps, forcing more reliance on Deebo Samuel and Brandon Aiyuk.
G Spencer Burford: Did not practice (knee/ankle) – Questionable; could weaken the interior offensive line.
DT Jordan Elliott: Did not practice (knee) – Questionable; impacts run defense depth.
LB Nick Martin: Did not practice (concussion protocol) – Questionable; affects linebacker rotations.
Other notes: The team has four players popping up mid-week, but core stars like QB Brock Purdy, RB Christian McCaffrey, and DE Nick Bosa are healthy and expected to play full snaps.
Indianapolis Colts:
WR Alec Pierce: Questionable (Achilles) – Limited practice; a deep-threat loss if out, shifting more targets to Michael Pittman Jr. and Josh Downs.
DT DeForest Buckner: Full participant (neck) – Expected to play; critical for stopping the run.
G Quenton Nelson: Full participant (wrist) – Good to go.
RB Ameer Abdullah: Full participant (knee) – Backup depth intact.
S Daniel Scott: IR (knee) – Out long-term.
Other notes: QB Anthony Richardson practiced fully and is cleared, along with 11 total players listed but mostly full participants. CB Ahmad “Sauce” Gardner was mentioned in one update, but that’s likely a cross-team error (he’s with the Jets); no impact here.
Player Matchups
This game features intriguing battles across both sides of the ball, pitting the 49ers’ balanced attack against the Colts’ explosive but inconsistent offense.
Brock Purdy (49ers QB) vs. Colts Secondary: Purdy is coming off a strong performance with 3 TDs and 295 yards against the Titans. He’ll face a Colts pass defense ranked 18th, which allows 220+ yards per game. Expect Purdy to target mismatches if Pierce is out, exploiting safeties with play-action to Samuel and Aiyuk.
Christian McCaffrey (49ers RB) vs. Colts Run Defense: McCaffrey leads the league in all-purpose yards, but the Colts rank 6th against the rush (allowing under 110 yards/game). LB Zaire Franklin and DT Buckner will key on stopping him inside, forcing the 49ers to go aerial.
Anthony Richardson (Colts QB) vs. 49ers Pass Defense: Richardson’s dual-threat ability (rushing TDs in recent games) meets a 49ers unit ranked 18th in pass defense but 10th in scoring allowed. CB Charvarius Ward and S Talanoa Hufanga could force turnovers if Richardson holds the ball too long.
Jonathan Taylor (Colts RB) vs. 49ers Linebackers: Taylor has rushed for 100+ yards in three of the last five games, but faces Fred Warner and the 49ers’ 12th-ranked run defense. This matchup could dictate the Colts’ ability to control the clock.
Nick Bosa (49ers DE) vs. Colts Offensive Line: Bosa’s pass rush (8.5 sacks this season) targets LT Bernhard Raimann and the Colts’ line, which has allowed pressure on 24% of dropbacks. If Burford is out for SF, the Colts’ edge rushers like Laiatu Latu could counter.
Team Records
San Francisco 49ers: 10-4 (3rd in NFC West)
Indianapolis Colts: 8-6 (3rd in AFC South)
Recent Team Forms
San Francisco 49ers (4-1 in last 5 games):
Week 15: W 37-24 vs. Tennessee Titans (Dec 14)
Week 14: W 26-23 vs. Los Angeles Rams
Week 13: L 19-30 vs. Tampa Bay Buccaneers
Week 12: W 26-8 vs. Cleveland Browns
Week 11: W 26-23 OT @ Los Angeles Rams The 49ers are on a hot streak, averaging 26.8 points per game in wins, with strong road performances (6-2 away).
Indianapolis Colts (3-2 in last 5 games):
Week 15: L 16-18 @ Seattle Seahawks (Dec 14)
Week 14: W 41-20 @ Tennessee Titans
Week 13: W 29-28 vs. Denver Broncos
Week 12: W 33-8 vs. Miami Dolphins
Week 11: L (specific score not detailed, but part of 8-6 record) The Colts have been solid at home (6-1) but inconsistent on offense, scoring 28+ in wins but under 20 in losses.
Series History
The Colts lead the all-time series 27-19 in 46 meetings (regular season only). The teams have split their last four encounters, with Indianapolis winning the most recent in 2021 (30-18 in Santa Clara). San Francisco has won 2 of the last 3 in Indianapolis, but the Colts hold a 15-9 home edge historically.
Betting Trends
49ers: 9-5 ATS overall, 5-1 ATS in last 6 games, 6-2 ATS on the road, 10-4 SU when favored. Over has hit in 8 of 14 games.
Colts: 8-5-1 ATS overall, 8-6 ATS in last 14, 6-1 SU at home, but 2-3 ATS as underdogs. Over has hit in 7 of 14 games.
Head-to-head: In the last 5 meetings, the underdog is 3-2 ATS, and games average 42 points (under trend).
49ERS NOTES:
• QB BROCK PURDY passed for 295 yards & 3 TDs for season-high 140.3 rating & had 44 rush yards in Week 15, his 7th career game with 140+ passer rating, tied-most (HOFer Kurt Warner) for most such games (min. 10 att. in each game) in 1st 4 seasons in NFL history. Has TD pass in all 6 games played this season. • RB CHRISTIAN MCCAFFREY had team-high 73 rush yards & TD in Week 15. Aims for 7th in row with 70+ scrimmage yards & 5th in row with TD. Ranks 3rd with 1,742 scrimmage yards & tied-3rd with 14 TDs this season & is 3rd player in NFL history (HOFer LaDainian Tomlinson – 6 seasons & Shaun Alexander – 5) with 1,600+ scrimmage yards & 13+ TDs in five career seasons. Had 173 scrimmage yards in last game vs. Ind. (12/22/19 w/ Car.). • WR JAUAN JENNINGS had team-high 2 TD catches last week & aims for 4th in row with TD reception. • WR RICKY PEARSALL led team with 96 rec. yards in Week 15. • TE GEORGE KITTLE had 8 receptions for 88 yards & TD in Week 15. Ranks tied-4th among TEs with 6 TD receptions this season. Has 7,864 rec. yards & 51 rec. TDs since 2017 & is 5th TE in NFL history with 7,500+ rec. yards & 50+ rec. TDs in 1st 9 seasons. • LB DEE WINTERS had 5 tackles & TFL in Week 15 & aims for 5th in row with 5+ tackles on road. • LB CURTIS ROBINSON had 7 tackles & 1st PD this season in Week 15 & has 6+ tackles in 3 of his past 4. • LB TATUM BETHUNE had 10+ tackles in 5 of his past 6 games. • DL KALIA DAVIS had 2nd PD this season in Week 15. • DB CLELIN FERRELL had 6 tackles in Week 15 & aims for 3rd in row with 6+ tackles. Has TFL in 2 of his past 3. • S MALIK MUSTAPHA led team with 10 tackles in Week 15 & aims for 4th in row with 7+ tackles. Has TFL in 2 of his past 3. Aims for 3rd in row on road with PD.
COLTS NOTES:
• COLTS rank 2nd in AFC in scoring offense (28 points per game). • QB PHILIP RIVERS completed 18 of 27 atts. (66.7 pct.) for 120 yards & TD in Week 15, 1st career start since 2020. Has 225+ pass yards & TD pass in 5 of his past 6 on MNF. Is 4-0 in 4 career starts vs. SF & has 250+ pass yards & 2+ TD passes in each start. • RB JONATHAN TAYLOR led team with 101 scrimmage yards (87 rush, 14 rec.) last week. Leads NFL in rush yards (1,443), rush TDs (16), scrimmage TDs (18) & ranks 2nd in scrimmage yards (1,761) in 2025. Has 120+ scrimmage yards in 4 of his past 5 at Lucas Oil Stadium. Has 95+ scrimmage yards & rush TD in only 2 career games on MNF. Had 110 scrimmage yards (107 rush, 3 rec.) & rush TD in last meeting. • WR MICHAEL PITTMAN has 6+ catches, 60+ rec. yards & TD catch in 2 of his past 3 on MNF. Had 4 catches for 105 yards & TD in last meeting. • WR JOSH DOWNS had TD catch in Week 15. Has TD catch in 2 of his past 3 at Lucas Oil Stadium. • TE TYLER WARREN ranks 2nd among rookies in receptions (63) & ranks 4th among TEs in rec. yards (718) in 2025. Is 1 of 3 rookies (Emeka Egbuka & Harold Fannin) with 10 games with 4+ receptions. Has TD catch in 3 of his past 4 at Lucas Oil Stadium. • LB ZAIRE FRANKLIN had 10 tackles & TFL last week. Has 10+ tackles in 4 of his past 5. Aims for his 7th in row on MNF with 9+ tackles. • LB GERMAINE PRATT had 10 tackles & TFL in Week 15. Has PD in 5 of his past 6. Has 8+ tackles in each of his 3 games at Lucas Oil Stadium this season. Aims for his 3rd in row vs. SF with 5+ tackles & PD. • DE LAIATU LATU had 3 TFL & sack last week. • S NICK CROSS had 7 tackles & 1st FF of season in Week 15. • S CAM BYNUM had 8 tackles last week. Has TFL & PD in 2 of his past 3.
Game Odds
San Francisco 49ers – 5.5
Indianapolis Colts 45.5
Odds Courtesy of Sports Odd Direct as of Sunday, December 21, 2025
