Goalkeeper Manny Agboola, 18, will be on the bench after being recalled from a loan spell at North Leigh.
Newcastle boss Rafael Benitez is likely to make changes again, as he did in the last round against Birmingham.
Striker Aleksandar Mitrovic (knee) and midfielder Jack Colback (illness) could return.
Oxford United manager Michael Appleton told BBC Radio Oxford:
"If we beat Newcastle, it would probably be as big a win for me as I've ever had as a manager.
"I remember being manager of Blackburn in the FA Cup fifth round and we went to Arsenal and became the only team to beat them in a FA Cup tie at the Emirates.
"That was some achievement as we probably spent about 80% of the game on the back foot. But for me, if Newcastle were in the Premier League right now, they'd be a top-10 team.
"They've got a fantastic manager, are a great club with a winning mentality and with fantastic support behind them."
Newcastle United boss Rafael Benitez:
"We knew we had to make changes [in the last round against Birmingham] because we have so many games.
"It is important to win, but using the squad and not taking too many risks with players was important. This competition is always difficult, but we will try to go through.
"When you play against any team at this stage, especially away from home, it gives them extra motivation."
Oxford United could hand a debut to striker Toni Martinez after his loan move from West Ham, but forward Chris Maguire (thigh) faces a fitness test.