Jones was initially reported as "questionable" to return, but his status was later downgraded.
"He didn't come back, so they worried it possibly could be a high-ankle (sprain)," head coach Kyle Shanahan said after the game. "So, that's what we've got to look into. Obviously, we're hoping it's not."
The Bills beat the 49ers 34-24 at State Farm Stadium in Glendale, Arizona, and San Francisco fell to 5-7 on the season.
Note: Article updated with post-game information from Kyle Shanahan.
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