The attacker, who only returned to action in Sunday's Premier League win over Tottenham Hotspur due to an injury picked up while playing at the Africa Cup of Nations in June, may have to sit out the midweek tie as a precautionary measure for a "non-serious muscle" problem.
It is believed he may have picked up the knock during the league match against Spurs.
"I've got players which have a few knocks and bruises. Joelinton has played when he was sore with a groin so he is a bit of a doubt. [Miguel] Almiron (ankle), [Fabian] Schar (knock), Jamaal [Lascelles] (calf), and [Christian] Atsu (muscle) are all doubts," Newcastle boss Steve Bruce said in his team news on Tuesday ahead of Wednesday's game, as reported by his club's official website.
"A few are carrying a few things so the one thing I can't do, as I've done with Allan [Saint-Maximin] is if there's a slight risk. We're waiting to let his hamstring settle.
"The initial scans say it isn't serious but we will not know the severity of it until later.
"I still expect to pick a team which is hopefully going to take us through [to the next round]."
On his injury comeback on Sunday, Atsu highlighted his importance to Newcastle with a sweet assist for Joelinton's match-winner over Tottenham.
Should he sit out Wednesday's tie, the 27-year-old will be expected to return to action in Saturday's welcome of Watford in the Premier League.