Fiorentina visit Rapid Vienna for a place in the Conference League and start M’Bala Nzola with Nico Gonzalez upfront, while Sofyan Amrabat and Luka Jovic are excluded amid transfer speculation.
It kicks off at the Allianz Stadion at 18.00 UK time (17.00 GMT) and the second leg will be at the Stadio Artemio Franchi next Thursday evening.
As per all UEFA knockout rounds now, the away goals rule no longer applies.
Last season, Fiorentina went all the way to the Final, losing 2-1 to West Ham United, so are eager to do even better this time around.
They had technically not qualified, but were bumped up after Juventus were excluded from UEFA competition for financial irregularities.
Amrabat and Jovic were not included in the squad for this play-off, while Jonathan Ikone and Abdelhamid Sabiri are injured, plus full-back Michael Kayode suffering from tonsillitis.
Nzola is preferred to the other summer signing Lucas Beltran and Josip Brekalo picked ahead of Christian Kouame.
Rapid Vienna smashed Debrecen 5-0 in the qualifying round, although it ended goalless on home turf and they ran riot in Hungary.
Defender and biggest summer signing Nenad Cvetkovic tore his anterior cruciate ligament at the weekend.
There is a lot of talent upfront with Marco Grull, Moritz Oswald and Matthias Seidl supporting veteran captain Guido Burgstaller.
Rapid Vienna: Hedl; Schick, M Hofmann, Querfeld, Auer; Kerschbaum, Sattlberger; Oswald, Seidl, Grull; Burgstaller
Rapid Vienna bench: Unger, Gartler, Greil, Strunz, Kuhn, Mayulu, Sollbauer, Koscelnik, Kaygin, Moormann, Bajic, Bajilicz
Fiorentina: Terracciano; Dodo, Milenkovic, Ranieri, Biraghi; Arthur, Mandragora; Gonzalez, Bonaventura, Brekalo; Nzola
Fiorentina bench: Christensen, Sottil, Beltran, Infantino, Mina, Martinez Quarta, Duncan, Comuzzo, Parisi, Amatucci, Kokorin, Kouame
Ref: Pajac (CRO)