Left wing-back Ben Chilwell, midfielders N'Golo Kante (knee) and Jorginho (hip), as well as versatile centre-back Trevor Chalobah (hamstring) are all ruled out with injuries, while midfielder Mateo Kovacic has tested positive for COVID-19.
With potentially no recognised left wing-back in Thomas Tuchel's squad, Saul Niguez could be handed a surprise start, after the German head coach previously suggested the Atletico Madrid loanee could be a "good fit" for this position.
Centre-back trio Andreas Christensen, Thiago Silva and Antonio Rudiger are expected to start once again, though Malang Sarr is also an option, while Ruben Loftus-Cheek could be handed his fourth successive start in centre-midfield.
In attack, Romelu Lukaku – who scored the only goal in September's 1-0 win against Zenit at Stamford Bridge – or Timo Werner are set to lead the line in attack, with Mason Mount, Callum Hudson-Odoi, Hakim Ziyech, Christian Pulisic and Ross Barkley to battle it out for a place in the starting lineup in an advanced midfield role.
Chelsea possible starting lineup: Mendy; Christensen, Silva, Rudiger; Azpilicueta, Loftus-Cheek, Saul, James; Mount, Ziyech; Lukaku