San Francisco 49ers at Indianapolis Colts Preview & Picks – Niners To Extend Streak On NFL Monday Night Football

leigh-copson
16 Dec 2025
Leigh Copson 16 Dec 2025
Share this article
Or copy link
  • San Francisco 49ers at Indianapolis Colts picks for Monday, December 22
  • Game is taking place at Lucas Oil Stadium
  • Preview, predictions, stats & form
(Getty Images)

San Francisco 49ers at Indianapolis Colts Preview & Picks

San Francisco are tipped to cover as they record a big road win on Monday night.

The 49ers head to Indianapolis in great form, winning and covering consistently, and they can take advantage of an out-of-form Colts team led by an over-the-hill quarterback.

  • San Francisco 49ers are on a 4-game win streak
  • San Francisco 49ers are 9-1-0 ATS in their 10 wins
  • Indianapolis Colts have lost each of their previous 4 games
  • The Over has cashed in 5 of San Francisco’s last 7 road games with 1 push

Head To Head

  • Indianapolis Colts lead the all-time series 27-18
  • Indianapolis Colts won 30-18 when the two teams last met in October 2021

San Francisco 49ers Form

San Francisco head out on the road riding a four-game win streak that took them to 10-4 – one game behind the Los Angeles Rams and Seattle heading into Week 16.

The 49ers raced out of the blocks by winning their first three games of the campaign, but they struggled for consistency in the weeks that followed.

They rebounded from a 26-21 loss to Jacksonville with a 26-23 overtime victory at the Los Angeles Rams, and then bounced back from a 30-19 defeat to Tampa Bay with a 20-10 win over Atlanta.

San Francisco failed to build on that as they lost 26-15 in Houston, and they were then unable to back up a 34-24 win against the New York Giants as they lost 42-26 to the Rams.

The 49ers have found some form since then though, backing up a 41-22 success at Arizona by beating Carolina 20-9, Cleveland 26-8 and Tennessee 37-24.

Indianapolis Colts Form

Indianapolis come into this game in desperate need of a win, having lost five of their last six games and each of the last four to fall to 8-6.

The Colts appeared to be storming to the playoffs when they won seven of their first eight games, but they failed to keep that momentum going.

They saw a four-game streak end with a 27-20 loss to Pittsburgh, and they have won just once game since that matchup back on November 2.

Indianapolis were unable to back up 31-25 overtime win against Atlanta as they lost 23-20 in overtime at Kansas City.

The Colts then fell 20-16 at home to Houston, before heading out on the road to lose 36-19 at Jacksonville and 18-16 in Seattle.

Verdict

Both teams are dealing with injuries, and both are heading in very different directions right now.

San Francisco are the team in form heading into this one, so we are taking the hotter hand.

Best Bet1: San Francisco -5.5 Spread @-111.11 at Stake.us - 4 Units
Best Bet2: Over 46.5 Total Points @-111.11 at Stake.us - 2 Units
San Francisco -5.5
Spread
@-111.11 - 4 Units
55 Stake Cash no deposit & 550,000 Gold Coins & 5% Rakeback
Use promo code NEWBONUS

Sign up with the code NEWBONUS. When you verify your account get 25 Stake Cash for free PLUS 250,000 Gold Coins and 5% Rakeback! No deposit required. Login each day for the next 30 days and get an additional 30 Stake Cash AND 300,000 Gold Coins. 21+ only. T&Cs apply. Excludes WA, NY, NV, ID, KY, MI, VT, NJ, DE, WV, PA, RI & MD.

Bet at Stake.us
Over 46.5
Total Points
@-111.11 - 2 Units
55 Stake Cash no deposit & 550,000 Gold Coins & 5% Rakeback
Use promo code NEWBONUS

Sign up with the code NEWBONUS. When you verify your account get 25 Stake Cash for free PLUS 250,000 Gold Coins and 5% Rakeback! No deposit required. Login each day for the next 30 days and get an additional 30 Stake Cash AND 300,000 Gold Coins. 21+ only. T&Cs apply. Excludes WA, NY, NV, ID, KY, MI, VT, NJ, DE, WV, PA, RI & MD.

Bet at Stake.us

Upcoming Events

27 March 2026

2026 MLB World Series Betting Preview Baseball 2026 MLB World Series Odds – LA Dodgers Favourites For 3-Peat

20 September 2026