The Owls are seven points from safety with six games to go, while Swansea are well placed in fourth after bringing an end to their losing run last time out.
Wednesday appeared to have revived their survival hopes with a rather extraordinary 5-0 win over Swansea's fierce rivals Cardiff City, scoring more than twice in a league game for the first time this season.
The Owls' biggest victory since January 2014 was supposed to provide a springboard to push on, but they instead fell to a disappointing 4-1 loss at Queens Park Rangers on Saturday afternoon.
It leaves Wednesday needing to make up a seven-point gap on the teams above them. With just 18 points to play for, this is very close to a must-win match for the Owls.
Worryingly for the Yorkshire side, though, they have only won one of their last five matches against Swansea in all competitions, losing three of those.
Swansea look to be in a far better place now on the back of their 3-0 win at Millwall last time out, bringing an end to a four-game losing streak without scoring.
Those defeats to Bournemouth, Cardiff City, Birmingham City and Preston North End left the Swans looking over their shoulder at the sides from seventh and below.
Automatic promotion is surely now out of the question, with a 10-point gap to make up on Watford in second, but Swansea can at least tighten their grip on a place in the playoffs should they make it back-to-back wins.
The Swans have won four of their last six league matches against teams from Yorkshire, although they did lose their most recent such match against Huddersfield Town 4-1 in February.
Lowe's brace in the win at Millwall ended a run of 15 consecutive Championship appearances without a goal for the forward.
There is no reason why Cooper will not stick with the same front two of Lowe and Ayew here, then, with Wayne Routledge the favourite to complete the attacking triumvirate.
As for the home side, they rather unsurprisingly named the same XI against QPR that started the victory over Cardiff.
However, after being routinely beaten in West London, Moore will surely make a change or two on Tuesday evening.
Sheffield Wednesday possible starting lineup:
Wildsmith; Harris, Lees, Borner; Palmer, Hutchinson, Bannan, Reach; Windass; Kachunga, Rhodes
Swansea City possible starting lineup:
Woodman; Naughton, Bennett, Guehi, Manning; Fulton, Grimes, Hourihane; Ayew, Routledge, Lowe
We say: Sheffield Wednesday 0-2 Swansea City
Wednesday desperately need to get some wins on the board if they are to avoid dropping into the third tier, while Swansea can take a huge step towards securing a top-six finish with all three points in Yorkshire.
The Owls may have thrashed Cardiff 5-0 last time out on home soil, but that is one of only two wins in their last 12 league outings, and they have a poor recent record in this fixture.