Jones-Drew (hamstring) and Shorts (groin) have not practiced all week and are expected to test their injuries on Friday, but coach Gus Bradley said there's a chance a decision on their chances of playing may not be made until just before kickoff.
"I think they're both very questionable," Bradley said Thursday. "We've got our fingers crossed on both of them."
Shorts has been battling a groin injury for much of the season and has managed it by not practicing on Wednesdays and being limited on Thursdays. That schedule got thrown off last week because the Jaguars played Houston on Thursday night and that wasn't sufficient time to rest his groin from the previous Sunday's game against Cleveland.
He played against the Texans but left the game late because of the pain. He's hoping the extra three days of rest between that game and Sunday's game against the Bills will be enough to allow his groin to improve.
"I've been dealing with it all year," Shorts said. "It's not getting better; it's getting worse.
"I think I'm going to go out there tomorrow and get some reps and stuff. We'll see how it feels tomorrow and then [make a] game-time decision as Gus said. If I'm able to play, I'm playing. No doubt about it. I have no problem dealing with pain but when it comes to your [groin] area, it's a little different."
Shorts leads the Jaguars in receptions (66), yards (77), and receiving touchdowns (three). If he is unable to play, Bradley said Kerry Taylor would start in his place. Taylor was signed on Nov. 4 from Arizona's practice squad and has caught three passes for 27 yards in four games.
Taylor would also be the team's kick returner if Jones-Drew is unable to play because regular kick returner Jordan Todman would start for Jones-Drew.
A third starter, safety Johnathan Cyprien, also did not practice Thursday because of a thigh injury. Bradley said he feels the best about Cyprien's chances of playing than any of the other injured players. Cyprien has started every game at strong safety this season and is second on the team with 83 tackles.