Exeter boss Paul Tisdale will be without defender Troy Archibald-Henville, who is suspended after picking up his fifth booking of the season in the midweek Johnstone's Paint Trophy win against Bristol Rovers.
Tisdale has no other suspension or injury concerns as the Grecians seek to put one over Alan Irvine's men.
First-team coach Rob Edwards said: "League One throws up some huge clubs and Sheffield Wednesday are no different.
"We've played plenty of them in League One and against some accomplished players.
"But we've done well at home in the last few years and we are delighted to be playing at home as it's been a long time. We are a decent home side and hopefully we can get a good result."
Sheffield Wednesday striker Neil Mellor could face a late fitness test.
Mellor, on loan from Preston, has missed the last two games due to an ankle injury and if he fails to make it then Clinton Morrison and Jermaine Johnson are expected to start up front again.
Lewis Buxton remains sidelined with a hamstring strain and fellow defender Jon Otsemobor is still struggling with a calf problem, so Daniel Jones is set to continue at right-back.
Midfielder Giles Coke will be sidelined for the next four weeks after undergoing minor knee surgery.
The Owls have won four of their last five league matches and climbed into the second automatic promotion place after last week's 6-2 home win over Bristol Rovers.