The winger was forced off early on with a foot injury during the the sensational 8-0 victory over Sheffield United on Sunday.
Immediately after the match, Newcastle boss Eddie Howe said: "It doesn't look too good. I think he has a toe problem. He pushed off and felt something in his toe.
"Early signs are there's probably an injury there, but we don't know what it is at the moment."
Barnes' injury has since been assessed with Howe confirming on Tuesday that Newcastle's summer signing faces 'months' on the sideline.
Howe said: "I think it's an injury to a part of the foot, just below the toe. I think it's quite a substantial injury.
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"We've had it scanned, we're now waiting on specialist opinion on what to do next and whether there's surgery involved, or not.
"I don't think it was a tackle, I think it was just pushing off to run.
"It's a very unusual injury - I won't go too technical because I'm not medically qualified to do so, but yeah, it's very unusual."
The winger arrived at St James' Park for a fee of £39million after joining from Leicester City.
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Since then he has made seven appearances for the club, scoring one goal.