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Cardinals at Colts prediction: Odds, expert picks, QB matchup, injury update, betting trends, and stats

Sunday afternoon the Arizona Cardinals (2-3) look to rebound from a brutal loss last weekend to the Tennessee Titans, but it will not be easy as they will be lining up against the top team in the AFC South, the Indianapolis Colts (4-1).

The Cardinals were outscored 16-0 in the second half against the Titans. Arizona did not score a point after the 10:43 mark of the second quarter. Emari Demercado looked to have scored early in the fourth quarter but did not hold onto the ball as he crossed the goal line. As a result, Arizona finds themselves looking up at everyone else in the NFC West. They sit a full two games behind the first-place 49ers.

The Colts continue to be one of the surprise stories of 2025. Last week they thumped the Raiders, 40-6. Jonathan Taylor ran for three scores and Daniel Jones threw for two as the Colts remained tied with Jacksonville atop the AFC South with their fourth win of the season.

Lets take a deeper dive into this Week 6 matchup between the Cardinals and the Colts.

NBC Sports has all the latest info and analysis you need, including how to tune in for kickoff, odds from DraftKings, player news and updates, and of course our predictions and best bets for the game from our staff of experts.

Game Details and How to watch the Cardinals at Colts live Sunday

  • Date: Sunday, October 12, 2025
  • Time: 1:00PM EST
  • Site: Lucas Oil Stadium
  • City: Indianapolis, IN
  • Network/Streaming: FOX

Want to check out the other games on the NFL schedule this week? We’ve got you covered right here on NBC Sports with all the matchup, venue, game-time and TV/streaming info so you won’t miss any of the action!

Game odds for the Cardinals at the Colts

The latest odds as of Sunday courtesy of DraftKings:

  • Moneyline: Arizona Cardinals (+275), Indianapolis Colts (-345)
  • Spread: Colts -7.0
  • Total: 46.5 points

This game opened at Colts -4.0 with the Game Total set at 47.5.

Be sure to check out DraftKings for all the latest game odds & player props for every matchup this week on the NFL schedule!

Did Gannon drop the ball on Demercado's fumble?
Mike Florio and Devin McCourty unpack the Jonathan Gannon-Emari Demercado interaction on the sideline following Demercado's unfortunate fumble at the goal line.

Quarterback Matchup for Arizona at Indianapolis

  • Cardinals Expected Starting QB: Kyler Murray
    Last Game: 10/5 vs. Tennessee - 23-31, 220yds, 0 TDs, 0 INTs, Sacked 3 times, 4 carries for 25yds
    Season: 5GP, 110-161, 962yds, 6 TDs, 3 INTs, Sacked 16 times, 29 carries for 173yds
  • Colts Expected Starting QB: Daniel Jones
    Last Game: 10/5 vs. Las Vegas - 20-29, 212yds, 2 TDs. 0 INTs, Was not Sacked, 1 carry for 2yds
    Season: 5GP, 107-150, 1290yds, 6 TDs, 2 INTs, Sacked 4 times, 19 carries for 56yds

Cardinals at Colts team stats, betting trends

  • The Cardinals have won 4 of their last 5 games against AFC teams
  • The Colts are 4-1 ATS this season
  • Game Totals in Colts’ games this season are 2-3 to the OVER
  • Game Totals in Cardinals’ games this season have gone 2-3 to the OVER
  • Arizona is 2-3 ATS this season

Cardinals Player Injuries

  • QB Kyler Murray (foot) is questionable for Sunday’s game
  • LG Evan Brown (hamstring) is questionable for Sunday’s game
  • DE Darius Robinson (pectoral) is questionable for Sunday’s game
  • CB Max Melton (hamstring) is questionable for Sunday’s game
  • LB Cody Simon (knee) is questionable for Sunday’s game

Colts Player Injuries

  • WR Alec Pierce (concussion) is questionable for Sunday’s game
  • DE Tyquan Lewis (illness) is questionable for Sunday’s game
  • CB Kenny Moore II (Achilles) is questionable for Sunday’s game
  • RB Tyler Goodson (groin) is questionable for Sunday’s game
  • LB Joe Bachie (undisclosed) was placed on IR on Wednesday and has been declared OUT for Sunday’s game
  • PK Spencer Shrader (knee) was placed on IR on Tuesday and has been declared OUT for Sunday’s game

Rotoworld Bet Best Bets

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Our model calculates projections around each moneyline, spread and over/under bet for every game on the NFL calendar based on data points like past performance, player matchups, stadium information and weather forecasts.

Once the model is finished running, we put its projection next to the latest betting lines for the game to arrive at a relative confidence level for each wager.

Best bets our model is projecting for this week’s game between the Cardinals and the Colts:

  • Moneyline: NBC Sports Bet is recommending a play on the Arizona Cardinals on the Moneyline.
  • Spread: NBC Sports Bet is leaning towards a play ATS on the Arizona Cardinals at +7.0.
  • Total: NBC Sports Bet is staying away from a play on the Game Total of 46.5.

Rotoworld has you covered with all the latest betting info & tools for NFL with player news, game predictions, player props, futures, and trends!

Follow our experts on socials to keep up with all the latest content from the staff:

● Jay Croucher (@croucherJD)
● Drew Dinsick (@whale_capper)
● Vaughn Dalzell (@VmoneySports)
● Trysta Krick (@Trista_Krick)