According to Tim Graham of The Buffalo News, he will not be returning to action against the Browns.
C.J. Spiller officially out for the rest of the game. Can't recall seeing somebody carted off the field and going back in.— Tim Graham (@ByTimGraham) Sept. 23, 2012
Losing both of them in the first three weeks of the NFL season could have huge repercussions for Buffalo's offense, and the pressure could fall on quarterback Ryan Fitzpatrick to produce in their stead.
Compound the loss of Jackson (who could miss another two weeks) with the injury to Spiller, and the Bills backfield looks bleak, at best.
More to the point, this offense could become one-dimensional.
Spiller has keyed much of Buffalo's offensive success over the first two weeks of the season. In fact, he led the league in yards-per-rush attempts with an astounding 10.1. Through the first two-and-a-half games, Spiller has accounted for 422 of Buffalo's 982 total yards on offense, or 42.97 percent of Buffalo's total offensive production.
Through two games, the Bills ran the ball 62 times and passed it 51 times. They know their running game is one of their best weapons, and they weren't afraid to use it. Now, though, without two dynamic runners, what will the Bills do?
Going forward, they likely will be taking to the skies much more than they have been through the first two weeks of the season. They are no strangers to relying on the pass under head coach Chan Gailey, having leaned heavily on their aerial attack throughout his tenure in Buffalo.
There's no denying, though, that the running game was essential to the Bills' success.
For that reason, the Bills should be keeping their fingers crossed that the injury to Spiller isn't serious. If they're without their two top running backs for an extended period of time, they could be in deep trouble.
Erik Frenz is the AFC East lead blogger for Bleacher Report. Be sure to follow Erik on Twitter and "like" the AFC East blog on Facebook to keep up with all the updates. Unless specified otherwise, all quotes are obtained firsthand.