Whoever earns a place in the quarter-finals will square off against either Basel or Eintracht Frankfurt.
With their place in the qualifying rounds of next season's competition having already been secured, Wolfsburg boss Oliver Glasner will feel that the pressure is off his side ahead of their trip to Ukraine.
Nevertheless, after a poor end to the Bundesliga campaign, Glasner will accept that he has a responsibility to deliver improved performances sooner rather than later.
Wolfsburg claimed just four points from their last four fixtures in Germany's top flight, and it exposed the gap which they have to make up to get anywhere near to the top four.
On a positive side, Glasner will feel that his players are well rested after their final league outing on June 27, something which could prove pivotal with many of the teams left in the competition having only recently concluded their domestic schedules.
Although that applies to Shakhtar, they have been confirmed as champions for some time, giving Luis Castro plenty of opportunities to regularly rotate his players.
Despite the changes in personnel, Shakhtar only dropped four points from 11 matches after the resumption, form which suggests that they should be full of confidence heading into Wednesday's encounter.
Antonio, who only turned 20 years of age in June, is becoming an increasingly influential figure in midfield, and the Brazil Under-20 international could potentially emerge as a key man for his side during the latter stages of this competition.
Shakhtar Donetsk Europa League form: WLW
Shakhtar Donetsk form (all competitions): WDWWWD
Wolfsburg Europa League form: LWWWWL
Wolfsburg form (all competitions): LWDLWL
Despite being linked with a move to the Premier League, Wout Weghorst will take his place in the Wolfsburg attack.
However, the visitors will be without right-back Kevin Mbabu, who has recently tested positive for coronavirus.
Renato Steffen could deputise for the Switzerland international, with Glasner potentially switching to a 3-4-3 formation.
Moraes should lead the line for the home side, but Antonio may find himself among the replacements.
Shakhtar Donetsk possible starting lineup:
Pyatov; Dodo, Krivtsov, Matvyenko, Cipriano; Marlos, Kovalenko, Stepanenko, Patrick, Taison; Moraes
Wolfsburg possible starting lineup:
Casteels; Pongracic, Brooks, Tisserand; Steffen, Schlager, Arnold, Roussillon; Mehmedi, Weghorst, Brekalo
We say: Shakhtar Donetsk 2-2 Wolfsburg
This has all the makings of a back-and-forth encounter, with Wolfsburg likely to benefit from the lack of crowd. However, despite temperatures expected to be as high as 30C, we feel that Shakhtar will have enough in the tank to see off opponents whose last league outing took place five weeks ago.