Both teams are running on short weeks, but the Eagles are at home and riding the momentum they accumulated in a big road win in Week 1.
The Chargers, on the other hand, are traveling three time zones over (they're 3-6 when doing so since the start of 2011) and coming off a demoralizing collapse in their home opener against Houston.
On paper, this is a matchup that should favor the Eagles in every way, but since we're so unfamiliar with both teams after big offseason transformations, anything can happen Sunday at Lincoln Financial Field.
Here's our final preview of the matchup, along with a prediction.
What Philly Must Do to Win, Offensive Edition
Take some shots. Wait, what? I'm really saying this? The new-look Eagles don't appear to be as pass-happy as Andy Reid's Eagles, but they have to try to stretch the Chargers out.
San Diego's run defense was extremely solid last season and did a good job against Arian Foster and Ben Tate Monday night.
Plus, this strategy will make things easier on LeSean McCoy, who was worked too heavily in the opener.
What Philly Must Do to Win, Defensive Edition
Dial up consistent pressure against Philip Rivers. Get in his head early and you're bound to win the turnover battle. This secondary is still very beatable, so you can't allow Rivers to get comfortable.
5 Most Important Non-Quarterbacks
DeSean Jackson: If they're going to take shots, Jackson will likely be the guy on the receiving end. Eric Weddle not included, that San Diego secondary sort of sucks.
Jason Peters and Lane Johnson: The Chargers still had 18 hurries against Houston and Michael Vick took too many hits against the Redskins. The onus is on the entire line, but the tackles have to step it up against Dwight Freeney and Jarret Johnson.
LeSean McCoy: He'll still be a factor regardless of how much his role decreases.
Cary Williams: With injuries thinning out an already iffy secondary, Williams has to lead the way and make some plays in coverage Sunday.
Injury Analysis, Eagles Edition
The Eagles are pretty healthy, except ESPN.com reports that the team won't have starting cornerback Bradley Fletcher on Sunday.
I'm not too worried, though, because second-year man Brandon Boykin might be just as good. He'll step in opposite Cary Williams and will likely flex back inside in nickel situations.
Still, that thin secondary means Vincent Brown could have some enticing matchups against Brandon Hughes or rookie Jordan Poyer in three-receiver sets.
Injury Analysis, Chargers Edition
Not a lot to report here either, other than ESPN.com's Bill Williamson suggesting that Manti Te'o is unlikely to play on Sunday with a foot injury.
B/R NFC East Blog Prediction
The Chargers are not a very good team. I mean, how do you choke like that in your home opener? I have no confidence in them on a short week coming across the country to play a team that is riding a ton of momentum.
Early on, it'll be hard to figure these Eagles out and I don't envision the Chargers being the first to solve the puzzle.
Eagles 27, Chargers 20