The Blades are looking increasingly likely to be relegated from the Premier League this term, and while the Owls are also in precarious position of their own, if they can manage to beat the drop, the two clubs will be fighting it out in the Championship next term.
Should they come face to face, it would be the first time that the two sides have met since March 2019, when they played out a 0-0 draw at Hillsborough.
In fact, that was the third consecutive Steel City stalemate that we had seen, and you have to go back to September 2017, when United beat Wednesday 4-2, for the last time that we got an actual winner between the two teams.
But of course, this is a rivalry that stretches back way beyond the past few years or so.
The first official meeting between the Blades and the Owls came in April 1891, with Wednesday winning 2-1.
In the years since, the sides have met on 143 other occasions, but who has had the better of the clashes, and how does it rank in terms of ferocity compared to some of the biggest rivalries in English football?
Paddy Power have ran the numbers, comparing win percentages from derby clashes between every Premier League club and their most fierce foes to determine which clashes truly are the most competitive.
Click and scroll through the pages below to read our countdown...