Gordon went off just before the half-time break at the Etihad Stadium after going down clutching the back of his leg.
He was unable to continue after being assessed by Newcastle’s medical staff, with more detailed scans set to take place in the next 24 hours.
Gordon is already a major doubt for Saturday’s home game with Brentford and next Tuesday’s trip to Tottenham, with his participation in the forthcoming FA Cup tie against Aston Villa and two-legged Champions League game against Qarabag far from certain.
“It looks like a hamstring problem,” admitted Howe. “I don’t quite know how bad it is, but it as enough for him to come off, so that’s a big worry.”
Harvey Barnes replaced Gordon, with Howe making three further substitutions at half-time, with his side trailing 3-0 on the night.
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Lewis Hall, Joe Willock and Nick Woltemade came off at the interval, with Kieran Trippier also making way in the second half, with Howe admitting he was keen to protect some of his key performers with the tie having already been effectively settled.
“It [protecting them] was definitely very much the thinking with Lewis and Joe Willock,” said Howe. “Lewis hasn’t had a rest – he’s been one we would have loved to have taken out at certain stages during this recent run of games we’ve had.
“We just felt this was the right time to do it, to make sure we can keep him at his best level for the next games coming up. I think he’s done really well to play the number that he has.
“It’s the same with Kieran, we’re trying to protect Kieran as we did at the end. And there’s other players that we’re trying to manage to. But obviously with the number of injuries we’ve got, we can’t do that as much as we would like. That’s where any injury to any player has a really detrimental effect.”