The U's are winless in their last four and sit in 18th in the EFL League One table while the Owls have only lost once in their last six and are just outside of the play-off places in seventh.
Jack Lankester has been ruled out for this matchup while Liam O'Neil's status is still being determined.
Sheffield Wednesday could welcome Saido Berahino back to the starting lineup after he was an unused substitute on the weekend. Josh Windass continues to recover from hamstring surgery and will miss out.
The Owls are also expected to be without Sam Hutchinson, Lewis Gibson, George Byers and Massimo Luongo.
Cambridge United: Mitov; Iredale, Jones, Masterson, Williams; May, Digby; Brophy, Hoolahan, Tracey; Ironside
Sheffield Wednesday: Wildsmith; Palmer, Dunkley, Iorfa; Brown, Wing, Bannan, Hunt; Dele-Bashiru; Gregory, Paterson
Ones to watch
Joe Ironside (Cambridge United)
The U's leading scorer with six goals, he's had a knack for providing Cambridge with big goals, scoring the equalizer against top of the table Plymouth Argyle in August as well as against Ipswich on Saturday to deliver a point to his side.
Lee Gregory (Sheffield Wednesday)
Grabbed the opening goal with a lovely finish into the bottom right corner before sending the goalkeeper the wrong way to double the Owls lead against AFC Wimbledon, giving him seven for the season. He also led the line well with some good touches and hold-up play.
How to watch
The match will not be shown on televison, but Cambridge is offering streaming coverage on their iFollow channel. Kick-off is set for 19:45 BST.