The 2-3 Arizona Cardinals will look to rebound from a brutal home collapse as they head to Lucas Oil Stadium to face the 4-1 Indianapolis Colts, and they ll have to do so without starting quarterback Kyler Murray.
The Colts hold several edges in this matchup, but the Cardinals possess one key advantage that points to a strong player prop opportunity. Find out who I like in my Cardinals vs. Colts predictions and NFL picks for today's game.
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Cardinals vs Colts prediction
Cardinals vs Colts Best bet: Marvin Harrison Jr. longest reception Over 22.5 yards (-108)
The Indianapolis Colts rank near the top of the NFL in almost every statistical category thus far this season. However, they do rank 30th in the league in defending deep passes — passes over 20 air yards downfield.
Marvin Harrison Jr. will be facing the team where his father is the all-time leader in receptions, receiving yards, and receiving touchdowns.
He's going to want to show out here in Indianapolis in honor of his father. He's also a big-time deep threat for the Arizona Cardinals to take advantage of that poor deep passing defense.
Harrison Jr. is averaging 15.3 yards per catch this season. He has also seen six targets of at least 20+ air yards this season. On those six targets, he has caught four for 136 yards, good for 34 yards per reception.
After a slow start to the season, MHJ has been heavily involved in the last two weeks. With them likely playing from behind, there should be multiple opportunities for Harrison Jr. to haul in a big catch.
Cardinals vs Colts same-game parlay
To add to my best bet, I am going to add the Over, as the Colts average 38 points per game when playing a defense in the bottom half of the NFL.
Finally, I am taking Tyler Warren to find the endzone. He has scored in each of the last two games.
- Marvin Harrison Jr. longest reception Over 22.5 yards
- Over 47.5
- Tyler Warren anytime touchdown
Our big-play SGP: Offense Aplenty
Michael Carter was the bell cow back last week, and I expect more of the same with all their injuries, and he will find the endzone.
- Marvin Harrison Jr. longest reception Over 22.5 yards
- Over 47.5
- Tyler Warren anytime touchdown
- Michael Carter anytime touchdown
Cardinals vs Colts game predictions
Cardinals vs Colts moneyline prediction
I don't expect another 30+ point blowout, but the Colts will beat another bad-to-mediocre team at home. Colts moneyline is a no-brainer, especially with Kyler Murray ruled out.
Cardinals QB Jacoby Brissett is expected to start Sunday in place of Kyler Murray, who is dealing with a foot injury, per me and @JFowlerESPN.
— Adam Schefter (@AdamSchefter) October 12, 2025
Brissett will make his first start for the Cardinals against the Colts, a team he played for from 2017-2020. pic.twitter.com/KWicOlo02D
Cardinals vs Colts spread prediction
I liked this Colts -7 spread a lot more earlier in the week when it was 5.5, but I will still lean with them here at 9.5 points now that Murray's been ruled out. This Cardinals defense will struggle to stop Daniel Jones and the Colts.
Cardinals vs Colts Over/Under prediction
Most of the sharp money is on the Over here, with 74% of the money on the Over despite only 41% of the bets.
Cardinals vs Colts odds
- Spread: Arizona +9.5 | Indianapolis -9.5
- Moneyline: Arizona +325 | Indianapolis -400
- Over/Under: Over 46 | Under 46
More NFL picks and odds from Covers
Cardinals vs Colts betting trend to know
The Colts have cashed the Over in 11 of their last 20 games. Find more NFL betting trends for Cardinals vs. Colts.
How to watch Cardinals vs Colts
| Location | Lucas Oil Stadium, Indianapolis, IN |
| Date | Sunday, October 12, 2025 |
| Kickoff | 1:00 p.m. ET |
| TV | FOX |
Cardinals vs Colts latest injuries
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