Cardinals vs. Colts Prediction, Odds, Spread, Injuries, Trends for NFL Week 6

Iain MacMillan | Oct 7, 2025

The Colts are home favorites against the Cardinals in NFL Week 6. / Grace Smith/IndyStar / USA TODAY NETWORK via Imagn Images

People keep waiting for the Indianapolis Colts to cool off, but all they do is keep winning, fresh off another dominant win against the Las Vegas Raiders. They'll look to stay hot in Week 6 when they welcome the Arizona Cardinals to town, who have lost three straight games.

The Cardinals got past the Panthers and Saints to start the season, but have lost three straight games in the final minutes of the past three weeks. Can they finally bounce back in Week 6? Let's find out what the oddsmakers think.

Cardinals vs. Colts Odds, Spread, and Total

Spread

• Cardinals +6.5 (-115)
• Colts -6.5 (-105)

Moneyline

• Cardinals +225
• Colts -275

Total

• OVER 47.5 (-105)
• UNDER 47.5 (-115)

Cardinals vs. Colts How to Watch

• Date: Sunday, Oct. 12
• Game Time: 1:00 pm ET
• Venue: Lucas Oil Stadium
• How to Watch (TV): FOX
• Cardinals Record: 2-3
• Colts Record: 4-1

Cardinals vs. Colts Betting Trends

• The UNDER is 5-1 in the Cardinals' last six road games
• Cardinals are 7-1 ATS in their last eight games vs. AFC opponents
• Cardinals are 6-2 ATS in their last eight games vs. AFC South opponents
• Colts are 4-1 ATS in their last five games
• The UNDER is 7-1 in the last eight meetings between these two teams

Cardinals vs. Colts Injury Reports

Cardinals Injury Report

• Kyler Murray, QB - Questionable
• Tip Reiman, TE - Out
• Darius Robinson, DE - Questionable
• Max Melton, CB - Questionable
• Evan Brown, C - Questionable

Colts Injury Report

• Spencer Shrader, K - Out
• Alec Pierce, WR - Questionable
• Kenny Moore II, CB - Questionable
• Tyler Goodson, RB - Questionable
• Grover Stewart, DT - Questionable

Cardinals vs. Colts Key Player to Watch

• Daniel Jones, QB - Indianapolis Colts

The career resurgence of Daniel Jones continues to be one of the most fascinating stories of this NFL season. He has completed 71.3% of passes for 1,290 passing yards, six touchdowns, and two interceptions. He has also added 56 rushing yards and three touchdowns on the ground. Is he this year's version of Sam Darnold from 2024?

Cardinals vs. Colts Prediction and Pick

The betting market is hesitant to start pricing the Colts as an elite team in the AFC, but I'm officially hopping on the hype train. Sometimes, some teams get off to unexpected hot starts, but their underlying metrics don't match their impressive record. That's not the case for the Colts. They rank third in the league in DVOA, second in EPA, fifth in opponent EPA, and fourth in Net Yards per Play.

Now, they host a Cardinals team that is in the bottom half of the league in virtually every metric, and Kyler Murray's days could be numbered. He has explosive plays at times, but he simply isn't consistent enough across four quarters of football. This team has found several ways to lose games, and they can't afford to do that against a team as good as the Colts.

Pick: Colts -6.5 (-105) via FanDuel

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