Milan are forced to completely transform due to a massive injury crisis, so Rafael Leao and Olivier Giroud are more important than ever against stuttering Chelsea.
It kicks off at Stamford Bridge at 20.00 UK time (19.00 GMT).
The Rossoneri are top of this Champions League group on four points and Chelsea bottom on one, but Stefano Pioli has a decimated squad.
Theo Hernandez, Davide Calabria, Simon Kjaer, Mike Maignan, Alessandro Florenzi, Alexis Saelemaekers, Zlatan Ibrahimovic and Junior Messias did not make the trip due to injury.
Divock Origi isn’t fully fit either, while due to squad restrictions, Yacine Adli, Malick Thiaw, Vranckx and Tiemoue Bakayoko are not registered for this competition.
In all, 12 players have been left behind, more than an entire line-up, and Ismael Bennacer is the fourth choice as captain.
Even more pressure is therefore on goalkeeper Ciprian Tatarusanu, with Sergino Dest as a makeshift right-back and Fode Ballo-Toure on the left.
Upfront are ex-Chelsea veteran Giroud and current Blues transfer target Rafael Leao, with Rade Krunic having to make do on the right alongside trequartista Charles De Ketelaere.
Chelsea have their own concerns, as N’Golo Kante is out of action, while Edouard Mendy, Marc Cucurella, Carney Chukwuemeka and Italy international Jorginho are carrying knocks.
There are starts for former Milan players Thiago Silva and Pierre-Emerick Aubameyang – who was in their youth academy – and ex-Inter man Mateo Kovacic.
For the first time since taking over as coach from Thomas Tuchel, Graham Potter gives former Napoli star Kalidou Koulibaly playing time.
Chelsea: Kepa; Fofana, Thiago Silva, Koulibaly; James, Kovacic, Loftus-Cheek, Mount, Chilwell; Aubameyang, Sterling
Milan: Tatarusanu; Dest, Kalulu, Tomori, Ballo-Toure; Tonali, Bennacer; Krunic, De Ketelaere, Leao; Giroud
Ref: Makkelie (NED)
yikes