The U's come into the game in 14th place having lost five of their last six, 10 points behind Wednesday who sit in third place, four points outside of the automatic promotion places.
Match preview
It has been a drastic downturn in form for Mark Bonner's Cambridge in recent weeks, with a victory at basement boys Morecambe the only exception on their dreadful run.
The U's have lost their last three in a row, including Saturday's 2-1 defeat at Bristol Rovers courtesy of a Greg Taylor own goal and a Josh Coburn strike either side of Joe Ironside's first-half equaliser.
They have now conceded 23 times this season, which is the third-worst record in the division - only Burton Albion and Forest Green Rovers have conceded more.
Cambridge have been good at home so far, picking up four wins in their six games at the Abbey, but did fall to a 2-0 defeat against Derby County the last time they hosted a League One game.
They will have to be at their best to beat a resurgent Wednesday side who have turned on the style in recent weeks.
Darren Moore's side have risen through the ranks thanks to a run of one defeat in six games, which came at the hands of league leaders Plymouth Argyle last Tuesday.
Wednesday bounced back last weekend in convincing fashion with a 3-0 victory at home to Cheltenham Town through Josh Windass's fourth of the season before two goals in the final seven minutes from Barry Bannan and Fisayo Dele-Bashiru secured the three points.
They have the second-best record away from home and have scored the second-most goals across the entire division and will be excited by the prospect of facing Cambridge's leaky defence.
Wednesday will need one of the top two to slip up this weekend to close the gap to the automatic promotion spots, but they can only finish the weekend in third place regardless of any results.
Cambridge United League One form:
L
L
W
L
L
L
Cambridge United form (all competitions):
L
W
W
L
L
L
Sheffield Wednesday League One form:
W
D
W
W
L
W
Sheffield Wednesday form (all competitions):
D
L
W
W
L
W
Team News
Cambridge are likely to be without midfielder Adam May, who picked up a knee injury in the week, which could see Jake Lankester start behind Ironside.
Left-back Harrison Dunk is touch-and-go but could feature on the bench, meaning Jubril Okedina could start for the third game in a row.
Wednesday could welcome George Byers and Mallik Wilks back into the matchday squad after both have been missing with injuries.
However, the game is too soon for Reece James, who joins Akin Famewo and Dennis Adeniran on the casualties list.
Cambridge United possible starting lineup:
Mitov; Okedina, Jones, Taylor, Williams; Brophy, Digby; Knibbs, Lankester, Smith; Ironside
Sheffield Wednesday possible starting lineup:
Stockdale; Palmer, Ihiekwe, Heneghan, Johnson; Vaulks, Bannan; Windass, Dele-Bashiru; Gregory, Smith
We say: Cambridge United 1-3 Sheffield Wednesday
Cambridge are in a big hole at the moment and it will be a struggle to get out of it against one of the in-form teams in the league.