The 2-3 Arizona Cardinals are coming off an embarrassing collapse at home and will be looking to bounce back on Sunday, October 12 when they travel to Lucas Oil Stadium to take on the 4-1 Indianapolis Colts.
My early Cardinals vs. Colts predictions and NFL picks expect the Colts offense to continue rolling and carry themselves to another big win.
Cardinals vs Colts predictions
Here are our early thoughts on the spread and total for this week’s game. We will have a full game preview (with a best bet and SGP) later in the week.
Early Cardinals vs Colts spread pick: Colts -5.5
After starting 2-0 with a couple of ugly losses against bad teams, the Arizona Cardinals have now lost three straight in dramatic fashion.
Their most recent loss to the Tennessee Titans was a travesty, as they were about to go up 28-6 when Emari Demercado dropped the ball early before crossing the goal line. They were outscored 16-0 from that point on.
The Cardinals defense is currently ranked 22nd in yards allowed per game and 28th in passing yards allowed per game. That is despite facing the likes of Spencer Rattler, Bryce Young, Mac Jones, Sam Darnold, and Cam Ward. Now they are about to face the third-leading passer in the league through five weeks.
Daniel Jones and the Indianapolis Colts bounced back in a big way from their first loss of the season by completely dominating the Las Vegas Raiders, 40-6. The Colts went back to not turning the ball over and scored six touchdowns in out of their eight drives.
Through five games, the Colts have only seven punts and three turnovers against 17 touchdowns. The Cardinals have either tied or lost the turnover battle in three of their five games this season. This game is not going to be a great opportunity for them to win the turnover battle, and they will especially struggle in stopping the Colts from moving the ball.
This might not be a blowout, but the Colts will still win by more than a touchdown.
Early Cardinals vs Colts total pick: Over 47.5
The Colts just continue to light up the scoreboard when they play a bottom-half defense and have averaged 38.0 points per game against those three teams. Now they get another bottom-half defense at home.
The Cardinals offense has struggled a bit this season with consistency, and they scored zero points last week against the Titans in the final 40:43 of game time. This is a bit concerning, as the Colts have twice scored nearly 80% of the points needed to hit the Over themselves, and the Under still hit because the opponent failed to reach double-digits.
However, the Cardinals have still scored at least 15 points in every game this season. Kyler Murray has been around middle of the pack in the league in passing yards, but he has 173 rushing yards and is averaging 6.0 yards per attempt.
While this game could end up another blowout like the other two games the Colts had where they failed to hit the game total Over despite scoring at least 33 points themselves, I do think the Cardinals will move the ball enough and make enough big plays to hit double-digits in the scoring department.
Cardinals vs Colts odds
- Cardinals vs. Colts spread: Colts -5.5
- Cardinals vs. Colts moneyline: Cardinals +200, Colts -240
- Cardinals vs. Colts Over/Under: 47.5
How to watch Cardinals vs Colts
- Cardinals vs. Colts matchup
- Date: Sunday, October 12, 2025, 1:00 p.m. ET
- City: Indianapolis, IN
- Venue: Lucas Oil Stadium
- TV: FOX
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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