Their opponents Cambridge United find themselves in 13th place in the League One table ahead of the game, and they will want to ensure they can avoid a late relegation battle by getting all three points on their travels.
Wednesday have been handed boosts with the returns of four players to training for this crucial tie in their push for the play-offs.
The Owls have suffered an injury crisis in the past few months, at one stage Darren Moore had an entire starting 11's worth of players unavailable to him.
It is unclear what stages Josh Windass, Nathaniel Mendez-Laing, Harlee Dean and Olamide Shodipo are at in their recoveries from injury, however all four of them trained with the first team in preparation for the game.
Dele-Bashiru and top scorer Gregory both played for 20 minutes off the bench against Lincoln City last Saturday, whether the two will now be fit enough to start on Saturday remains unclear.
U's boss Mark Bonner confirmed in his press conference that this would be the first time in months that he will have more than the matchday squad of 18 available to him.
Bonner also said that Liam O'Neil has returned to training ahead of the game.
The Irishman is therefore a step closer to being in contention to play even if he does not pass a fitness test for the game against The Owls.
Kai McKenzie-Lyle is also back on the grass, but is not expected to be available for this fixture.
Joe Ironside also played his first game since January 18 when he started against Shrewsbury last time out for The U's.
Peacock-Farrell, Storey, Hutchinson, Palmer, Johnson, Bannan, Luongo, Byers, Hunt, Gregory, Berahino.
Mitov, Williams, Okedina, Jones, Dunk, May, Digby, Smith, Hoolahan, Brophy, Ironside.
The Owls had won seven of their last eight games before their surprising 3-1 defeat against The Imps last Saturday.
It has been a great run for Wednesday with the occasional slip-up, but losses to sides like Lincoln could well prove costly for Moore and his players come the end of the season.
Wednesday will be hoping that they can get an important win to put themselves back on track as they search for a way back into the play-off places.
The U's have struggled of late and are winless in their last three, losing two of them.
The Yellows had also conceded seven goals in their last two games before drawing 0-0 against Shrewsbury Town, but Bonner's side have also kept three clean sheets in their last five games.
Cambridge have been very unpredictable defensively in recent games, and Bonner and his side will know that they will have to produce a solid defensive performance should they want to leave Hillsborough with anything on Saturday afternoon.
Their recent away form leaves a lot left to be desired also, as they have lost four of their last five on their travels, coming from behind twice to secure a point against Burton Albion in a 2-2 draw in the other game.
Ones to watch
The chance for top scorer Lee Gregory to make his first start for The Owls since Wednesday's 3-2 loss against Oxford United on January 22 will be exciting for Moore and the Wednesday fans.
Gregory, who has scored eight times for the club this term, will have good support around him as well, as Moore will be able to choose from Saido Berahino and Callum Paterson to support Wednesday's talisman up front.
Whether or not he will be able to start for The Owls is still unknown, but he will be hoping to add the clinical edge to the Wednesday side who have often struggled to finish off chances during the Englishman's absence.
Sam Smith has netted 11 times for The U's this season and will provide a threat to Wednesday's defence who were exposed last week by John Marquis, who scored a brace and assisted against a shaky Owls backline.
The Mancunian has not scored in his last two games, but scored five in four before that, including a brace against Oxford, which The Yellows lost 4-2.
Smith will be hoping to get himself back amongst the goals at Hillsborough on Saturday to try and turn his side's recent form around.
Historically, the head to head favours The Owls, who have won nine meetings between the two sides compared to four wins for Saturday's visitors and four draws.
However, in recent history matches between Wednesday and Cambridge have seen more wins for The U's than Moore's side.
The Owls have not beaten Cambridge since a 1-2 win against them in the FA Cup in January 1993.
Where to watch
Sheffield Wednesday and Cambridge fans based in the UK and Ireland can use iFollow on both club websites and pay £2.50 for an audio match pass to listen to live updates from the game. Those abroad can purchase a match pass to watch a live stream of the game.
Highlights will be available from the game by the end of the day at the latest.
What the managers have said
Ahead of the game, Cambridge United manager Mark Bonner spoke highly of his opponents and the squad The Owls have access to.
He said: “They’ve got incredible depth, as well as some real quality in their team. We know how hard it will be as well as the level they can get to, they can be ruthless.
"Despite all that, we've got that experience that we know we can come out on top like we have in some big games this year."
Bonner also said that he believed Wednesday will want to bounce back from their defeat against Lincoln, and praised Owls boss Darren Moore, calling him an 'excellent manager'.