Wide receiver Cecil Shorts III (groin) and guard Will Rackley (concussion) were also inactive Sunday.
Jones-Drew (hamstring) leads the Jaguars with 719 yards rushing, while Shorts is the top receiver with 66 catches for 777 yards. Rackley has started 11 games this year.
The Jaguars will also be without strong safety Johnathan Cyprien (thigh). The rookie had played every down on defense in Jacksonville's 13 games.
No starters were among Buffalo's seven inactives. The list included quarterback Jeff Tuel, defensive backs Jonathan Meeks and Brandon Smith, running back Ronnie Wingo, guards Mark Asper and Antoine McClain and tight end Tony Moeaki.
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