LeSean McCoy
LeSean McCoy was the NFL's leading rusher last year. Reuters

The Indianapolis Colts will look to rebound from a tough road loss in the season opener when they host the Philadelphia Eagles on Monday night at Lucas Oil Stadium. The Colts were dealt a harsh blow last week, as the defense will be without arguably their best player.

Robert Mathis, who led the league in sacks (19.5) in 2013, will be sidelined for the season with an Achilles' tendon injury. Mathis’ absence will likely be felt against the high-tempo Eagles offense, which scored 27 points against the Jacksonville Jaguars in the season opener and totaled 420 yards.

"We have to move on, and he'd be the first one to tell you that we just have to move on and win games," said outside linebacker Bjoern Werner of Mathis, to USA Today. "I mean, the note meant a lot already, you know, because of his suspension. But now, with this, it really makes you realize what you have. Everyone in this locker room knows it's hurting Robert Mathis a lot. It hurt him enough to be out with the suspension, but now not to be here the whole year? We have to be there for him. He was always the guy that had been there for everyone else, but now the whole season... We have to be there for him."

In the loss to the Denver Broncos on Sunday night, the Colts defense sacked quarterback Peyton Manning just once. Manning completed 22 of his 36 pass attempts for 269 yards. The Colts defense allowed 24 points in the first half before limiting the Broncos to just seven points in the second half. The unit will be tested on national television again on “Monday Night Football.”

The Eagles boast an offense that can dominate on the ground and in the air. Quarterback Nick Foles threw for 322 yards off 27 completions against the Jaguars with Jeremy Maclin perhaps taking over the top wide out role after DeSean Jackson’s exit. Meanwhile, the duo of LeSean McCoy and Darren Sproles might be the most effective rushing tandem in the NFL. They combined for 10 receptions and 145 rushing yards in the home win.

The Colts boast an impressive offense of their own. Andrew Luck threw for 370 yards on 53 pass attempts. Reggie Wayne appears to still be in fine form. The six-time Pro Bowler had nine receptions for 98 yards.

The running game will look to rebound against the Eagles. Trent Richardson and Ahmad Bradshaw combined for just 35 yards on nine carries. Both running backs are coming off forgettable 2013 seasons, with Bradshaw missing most of the season with a neck injury.

The Eagles defense will be facing tougher competition after hosting Jacksonville. Quarterback threw for 266 yards and the defense failed to force a turnover until the final two minutes when Fletcher Cox recovered the ball and ran it 17 yards for a touchdown.

Both teams enter the game with injuries, though the Colts have it worse. Wide receiver/returner Josh Huff and backup tackle Matt Tobin are out, while running back Chris Polk, wide receiver Brad Smith and cornerback Jaylen Watkins are expected to play for Philadelphia. Joining Mathis on the Colts sideline is top linebacker Jerrell Freeman, who is out with a hamstring injury.

Betting Odds: Colts favored by 3 points

Over/Under: 54 points

Kickoff Time: 8:35 p.m. ET

TV Channel: ESPN

Live Stream: WatchESPN

Prediction: Eagles over Colts, 31-28

An IBTimes staff reporter contributed to this report.