Wilshere suffered an ankle injury during Friday night's 4-0 victory over Coventry in the fourth round of the FA Cup.
The Premier League pacesetters will have defender Thomas Vermaelen and midfield duo Mikel Arteta and Aaron Ramsey available for the match at St Mary's though.
"We have a doubt about Jack Wilshere, who had this ankle problem during the game against Coventry," Wenger said.
"But we have three players back normally in the squad. The three are Vermaelen, Arteta and Ramsey.
"They should all be back and available, but we might lose Jack for tomorrow's game. "
Arsenal's victory over Coventry has set them up with another home tie in the FA Cup, this time against Liverpool.
"It's an interesting draw and a difficult one. We have a little advantage by playing at home. That means we don't travel," Wenger added.
"But overall it's a great difficulty, and we'll try again to absorb it and to come out in a positive way."
The fifth-round tie at the Emirates is due to be played on the weekend of 15 and 16 February.