Milan need to get back on track in Serie A after a surprise defeat to Torino, as Brahim Diaz, Rafael Leao and Divock Origi host Spezia.
It kicks off at San Siro at 19.45 GMT.
The Rossoneri thrashed RB Salzburg 4-0 midweek to secure their place in the Champions League Round of 16 after almost a decade away.
However, they need to focus back on Serie A now, having suffered a shock defeat to Torino last time out, ending a run of four straight wins.
The injury list remains extensive, with Mike Maignan, Davide Calabria, Zlatan Ibrahimovic, Alexis Saelemaekers and Alessandro Florenzi out.
Brahim Diaz returns to the starting XI with Leao and Origi, while Sandro Tonali is rested.
Spezia are missing suspended Dimitrios Nikolaou, with Emmanuel Gyasi, Simone Bastoni and Viktor Kovalenko injured, but have Daniel Maldini in the squad.
They have picked up just one point from the last five rounds and lost all six away games without scoring a single goal.
This fixture has gone down in history for last season’s controversial denouement.
Junior Messias had scored to put Milan 2-1 up in stoppages, but the referee blew the whistle too early for a free kick, not giving the advantage.
From that free kick, Spezia then went on the counter-attack and scored for a 2-1 victory, leaving the Rossoneri and especially the official distraught at this honest, but costly mistake.
Milan: Tatarusanu; Kalulu, Gabbia, Tomori, Theo Hernandez; Krunic, Bennacer; Messias, Brahim Diaz, Leao; Origi
Spezia: Dragowski; Ampadu, Caldara, Kiwior; Holm, Bourabia, Ekdal, Agudelo, Amian; Maldini, Nzola