McClean picked up an ankle injury during Republic of Ireland's 2-0 victory over Poland on Wednesday night and O'Neill has admitted that it may prevent him from featuring against the Gunners.
O'Neill told reporters: "We have a problem with James McClean, who picked up an injury during the course of the game.
"He hurt himself in the first half, but continued in the second half and came off after, I think, 80 minutes in the match and arrived here, where his ankle is particularly swollen. That's causing us some concern at the moment."
McClean has scored five goals in 31 appearances for Sunderland this season.