Colts vs. Titans odds, picks, prediction, spread, line: Start time, betting preview, best bets for NFL Week 6

The winless Tennessee Titans head north to Indianapolis to take on the Colts in Week 6 of the NFL season. It's been a dismal season for Tennessee with pressure mounting to get quarterback Cam Ward going. The Colts (2-3) come off a road loss in Pittsburgh. Kickoff for this AFC South matchup is set for 1 p.m. ET. The Colts are 7-point road favorites at DraftKings Sportsbook, and the Over/Under is 44.5.

We'll break down the latest Colts vs. Titans odds from DraftKings and deliver our best bets for the contest with help from the SportsLine Projection Model. The model, which simulates every NFL game 10,000 times, is up more than $5,000 for $100 players on betting sites on top-rated NFL picks since its inception. The model entered Week 6 of the 2026 NFL season on a 57-46 run on top-rated picks dating back to 2024.

Colts vs. Titans betting odds (via DraftKings)

Colts vs. Titans money line: Colts -340, Titans +270 Colts vs. Titans over/under: 44.5 (Over -108, Under -112) Colts vs. Titans spread: Colts -7

Colts vs. Titans betting preview

With all due respect to Colts and Titans fans, this is a game for the sickos. Tennessee has scored the fewest points in the NFL. They average 11.6 per game -- a depressing number. This is the sort of campaign that gets people fired and puts quarterbacks on top of draft boards.

In short, Tennessee is the exact sort of opponent the 2-3 Colts want to see coming to town. Indianapolis is a weird team. The Colts managed to hang tough with the Chiefs and blew the doors off the Commanders on the road but couldn't hang with the mediocre Steelers in Week 5. The Alec Pierce injury continues to hang over the Indy offense, but this remains a top-half attack and Indy will always have a chance as long as Jonathan Taylor remains healthy. Even with Pierce still on the shelf, Daniel Jones should feel confident this weekend. Tennessee has allowed a 74% completion rate to its opponents, the second-worst mark in the league.

But the Titans may also have something to be excited about. Indianapolis has fielded the sixth-worst run defense in the league thus far, which could lead to some success for Tony Pollard (and Cam Ward, who leads his team in rushing touchdowns).

Colts vs. Titans picks, prediction

Over 44.5