The soon-to-be Chelsea attacker, who was a substitute in Leipzig's 1-1 first-leg draw three weeks ago after recovering from a knee injury, picked up a fresh hamstring problem in Die Roten Bullen's defeat to Borussia Dortmund on March 4.
Xaver Schlager was also a casualty of that contest with an ankle ligament injury, which could rule him out for the rest of the season, while Peter Gulacsi and Abdou Diallo also remain sidelined.
Gulacsi's continued recovery from an ACL injury means that Janis Blaswich will hold the fort in goal, as Willi Orban and the much-coveted Josko Gvardiol start in the heart of the backline.
Marcel Halstenberg set up Gvardiol's first-leg equaliser and should feel confident of displacing David Raum, while Benjamin Henrichs can expect to fend off the threat of Lukas Klostermann, who was an unused substitute in Saturday's win over Borussia Monchengladbach following an illness.
With Schlager absent, Amadou Haidara can look forward to forming the double pivot with Konrad Laimer - who is expected to join Bayern Munich in the summer - as Emil Forsberg starts in the number 10 position.
Forsberg should form an unchanged attacking quartet with Dominik Szoboszlai, Timo Werner and Andre Silva, but Dani Olmo is another option, having recovered from a muscle problem to come on as a late substitute at the weekend.
RB Leipzig possible starting lineup: Blaswich; Henrichs, Orban, Gvardiol, Halstenberg; Laimer, Haidara; Szoboszlai, Forsberg, Werner; Silva