The sides played out an entertaining 2-2 draw in Serbia last week. Milan Pavkov netted deep into stoppage time to deny the visitors an away win. Belgrade played with 10-men for the final quarter.
The Rossoneri now face a must-win game at home but form is not on their side at the moment. On either side of the first-leg slatemate, Stefano Pioli's men were routed by Spezia and Inter Milan in the league.
These back-to-back defeats led to them ceding top spot in Serie A. They now trail the Nerazzurri by four points in the title race, having once seemed favorites for the Scudetto.
The Stars will hope to pounce on their vulnerability and create a huge upset, though they've never beaten Milan in five meetings.
AC Milan vs Red Star Belgrade Head-To-Head
In five encounters between the sides, AC Milan have beaten Red Star twice - both coming in Champions League qualifiers during the 2007-08 season.
That includes a 1-0 home victory. The only previous encounter at the San Siro came back in the 1988-89 season, which ended 1-1.
AC Milan Form Guide (all competitions): W-W-L-D-L
Red Star Belgrade Form Guide (all competitions): D-W-W-D-W
AC Milan vs Red Star Belgrade Team News
The home side will be without Mario Mandzukic, Daniel Maldini, and Ismael Bennacer due to injuries. Meanwhile, Zlatan Ibrahimovic is doubtful for the clash after develping calf problems in the derby defeat at the weekend.
Injured: Zlatan Ibrahimovic, Mario Mandzukic, Daniel Maldini, and Ismael Bennacer
Red Star Belgrade
Aleksandar Katai is a long-term absentee, having been sidelined with adductor problems since November. Meanwhile, Strahinja Erakovic has been injured since earlier this month.
Milan Rodic is suspended from the clash after getting sent off in the first leg.
Injured: Aleksandar Katai and Strahinja Erakovic
Suspended: Milan Rodic
AC Milan vs Red Star Belgrade Predicted XI
AC Milan (4-2-3-1): Gianluigi Donnarumma; Davide Calabria, Simon Kjaer, Alessio Romagnoli, Theo Hernandez; Sandro Tonali, Franck Kessie; Alexis Saelemaekers, Hakan Calhanoglu, Ante Rebic; Rafael Leao.
Red Star Belgrade (3-4-1-2): Milan Borjan; Radovan Pankov, Nemanja Milunovic, Milos Degenek; Marko Gobeljic, Guelor Kanga, Njegos Petrovic, Zeljko Gavric; Mirko Ivanic; El Fardou Ben, Diego Falcinelli.
AC Milan vs Red Star Belgrade Prediction
Milan desperately need a win in this game. Despite all their injuries, we believe they have the might to see off Belgrade and advance to the next round.
Prediction: AC Milan 3-1 Red Star Belgrade