The Colts come off a 24-17 loss to the Titans and now sit at 1-2-1, while Denver helped give the Raiders their first win of the year 32-23, and are now 2-2 on the season.
Neither team has lived up to expectations so far this year, and a win on Thursday night would go a long way for both organizations just from a mental side of things.
The Broncos just lost second-year running back Javonte Williams for the season after he suffered a torn ACL against the Raiders, and this comes after Denver was held to just 85 yards rushing in their loss to Vegas.
More responsibility will clearly rest on Russell Wilson now, who's part of an offense that ranks just 19th in passing yards per game, but considering how much they paid Wilson, it's probably time Nathaniel Hackett opened things up a bit for his new franchise quarterback.
Denver averages just 16.5 points per game and is just 1-3 ATS so far.
With both teams working on a short week, injuries will play even more of a key factor in this game, and Indy is still monitoring Jonathan Taylor's status for Thursday night against the Broncos with an ankle injury.
After leading the league in rushing yards last year, Taylor ranks sixth with 328, on a Colts team that was the favorite to win the AFC South, but instead sits third through the first four weeks of the season.
A hobbled Taylor will be another key factor leading up to this game, so keep an eye on that.
With all their issues, the Colts are still sixth in rushing yards allowed per game, and with the Broncos losing Williams for the year and Melvin Gordon not 100 percent either, this can be an advantage for Indy to capitalize on.
Colts +3.5 is the lean here.