Sheff Wed head into the bank holiday weekend's action top of the table on goal difference, while Oxford are only one position and three points above the relegation zone.
Match preview
Having finished inside League One's top eight positions in each of the past three seasons - missing out on promotion via the playoffs in subsequent campaigns between 2019 and 2021 - few people could have foreseen Oxford fighting against relegation this time around.
However, that is exactly the position which the U's find themselves in, with a measly return of three points from their last 12 matches unsurprisingly seeing them edge closer to the drop zone.
Two of those points have been collected in their last two matches, though, suggesting that Liam Manning may slowly be turning things around after replacing Karl Robinson in the managerial dugout last month.
Indeed, securing a 0-0 draw away to playoff contenders Peterborough United exceeded all expectations from their trip to the Midlands on Saturday, with Manning's side restricting their dangerous opponents to only three shots on target across the course of the encounter.
It may not be a bad time for them to play the league leaders, either, considering that Sheffield Wednesday are on a five-match winless streak themselves, but Oxford will undoubtedly require another diligent performance if they are to avoid defeat.
After winning five consecutive matches, Sheffield Wednesday looked set to romp away with the League One title this season, but two defeats and three draws in the five games since have seen Darren Moore's side squander control of their own destiny.
Both Plymouth Argyle and Ipswich Town head into the weekend's action within two points of the Owls, having each played one game fewer than them, meaning that even winning every match between now and the end of the season would not absolutely guarantee Sheff Wed's automatic promotion back to England's second tier.
However, there will almost certainly be more twists and turns to come between now and next month, with Moore hoping that his side's blip is now over after their latest dropped points came at home to Lincoln City on Saturday in the form of a 1-1 draw.
The former Derby County defender will be confident of piling on the misery for their forthcoming opponents on Friday, even if he will almost certainly hold plenty of respect for the work that Manning has done as a manager at this level, both with Oxford and more notably Milton Keynes Dons.
Only victory at the Kassam Stadium will be enough to ensure that Sheffield Wednesday remain top of the table beyond Easter Sunday ahead of hosting another relegation-threatened side in the shape of Accrington Stanley on Monday.
Oxford United League One form:
L
L
L
L
D
D
Sheffield Wednesday League One form:
W
D
L
L
D
D
Team News
Oxford welcomed youngster Stephan Negru back to their matchday squad away to Peterborough at the weekend, with the defender recovering from a recent ankle issue to be named among the substitutes.
Manning is unlikely to see any reason to make changes after claiming a highly creditable draw away to Posh, meaning that Josh Murphy should retain his place on the right flank.
Sheffield Wednesday, meanwhile, are a similarly-settled unit under Moore's tutelage, with the former West Bromwich Albion boss unlikely to be panicked by his side's recent lack of wins.
Lee Gregory and Michael Smith, who scored the opener against Lincoln on Saturday, remain a highly potent offensive duo, meaning that Mallik Wilks may have to remain patient from the bench.
Oxford United possible starting lineup:
Eastwood; Long, Moore, Findlay, Brown; McGuane, Brannagan; Murphy, Browne, Wildschut; Joseph
Sheffield Wednesday possible starting lineup:
Stockdale; Palmer, Iorfa, Flint, Famewo, Johnson; Bannan, Vaulks, Adeniran; Gregory, Smith
We say: Oxford United 1-2 Sheffield Wednesday
Despite there being 19 places and 42 points between these two sides heading into Friday's encounter, Oxford have shown signs of trending in the right direction under Manning's stewardship in their last two matches.
However, Sheffield Wednesday's winless run surely cannot continue much longer, and we expect them to claim a tight victory to remain top of the table.