Jorginho runs the Chelsea midfield, but Romelu Lukaku is not fit enough to start, while Juventus look to Federico Chiesa and Alvaro Morata upfront.
It kicks off at Stamford Bridge at 20.00 GMT.
Juve have already booked their spot in the Round of 16, but this is a head-to-head for top spot and in theory a better draw going forward.
Giorgio Chiellini, Danilo, Mattia De Sciglio, Aaron Ramsey and Federico Bernardeschi are out of action, with Paulo Dybala nowhere near fully fit.
It means Chiesa is again used as a forward with Morata, supported this time by Weston McKennie in a wider role, returning Juan Cuadrado and Alex Sandro to full-backs.
Dejan Kulusevski is only on the bench after having dental surgery this week.
Chelsea miss former Inter midfielder Mateo Kovacic, while ex-Nerazzurri striker Lukaku is still nursing an ankle sprain.
Timo Werner isn’t fully fit either, so Christian Pulisic is the False 9 flanked by Hakim Ziyech and Callum Hudson-Odoi, with Jorginho and N’Golo Kante pulling the midfield strings.
There are plenty of ex-Serie A players in the side, including former Milan defender Thiago Silva and ex-Roma centre-back Antonio Rudiger.
Chelsea: Mendy; Chalobah, Thiago Silva, Rudiger; James, Kante, Jorginho, Chilwell; Ziyech, Pulisic, Hudson-Odoi
Chelsea bench: Kepa, Bettinelli, Alonso, Christensen, Lukaku, Werner, Loftus-Cheek, Saul Niguez, Barkley, Mount, Azpilicueta, Sarr
Juventus: Szczesny; Cuadrado, Bonucci, De Ligt, Alex Sandro; McKennie, Bentancur, Locatelli, Rabiot; Morata, Chiesa
Juventus bench: Pinsoglio, Perin, Arthur, Dybala, Kean, Rugani, Kulusevski, De Winter
Ref: Jovanovic (SRB)
It would be so ironic if Chelsea were awarded a penalty kick in the dying stages and Jorginho were to take it and score convincingly.