Lazio use Matteo Cancellieri as a False 9 in the absence of Ciro Immobile, as they seek revenge against Midtjylland for the 5-1 defeat and target Europa League progress.
It kicks off at the Stadio Olimpico at 17.45 UK time (16.45 GMT).
The Biancocelesti are flying high in Serie A in third place and kept six straight clean sheets there, but in Europe it has been a very different experience.
Their lowest ebb was a 5-1 defeat in Denmark on September 15, but they are saved by the fact this is a perfectly balanced group, with all four teams on five points.
Immobile is injured and Manuel Lazzari suspended, so Cancellieri is the False 9 with Sergej Milinkovic-Savic as support.
Junior Brumado is out injured for Midtjylland, who held Feyenoord 2-2 in both their meetings.
Lazio: Provedel; Hysaj, Gila, Romagnoli, Marusic; Milinkovic-Savic, Marcos Antonio, Basic: Felipe Anderson, Cancellieri, Zaccagni
Midtjylland: Lossl; J Andersson, Dalsgaard, Sviatchenko, Paulinho; Martinez, Charles, Evander; Isaksen, Dreyer, Chilufya
Ref: Stefanski (POL)