Manchester City manager Manuel Pellegrini will possibly have to make do without star forward Sergio Aguero and Brazilian midfielder Fernandinho as both face a race to be fit due to physical problems, while Samir Nasri could make the bench after resuming training.
James Milner will have to watch the game from the stands after picking up a one-match ban following his three yellow cards in the group stages.
For Barcelona, experienced defender Carles Puyol and Brazil international Neymar are expected to be match fit in time after resuming regular training action this week, but neither of the two has featured for the Catalans in recent weeks.
Mexico international Jonathan dos Santos will miss the game as he is still recovering from a cruciate ligament injury.
Promising midfielder Emre Can will skip Tuesday's encounter versus the Ligue 1 champion due to suspension after picking up his third yellow card of the campaign against Real Sociedad.
Stefan Reinartz is also unlikely to feature due to injury, while Australia international Robbie Kruse is unavailable due to his knee problems.
PSG coach Laurent Blanc will be without Uruguay star Edinson Cavani after he was ruled out for three weeks with a thigh strain and Christophe Jallet is also unavailable.
Youngster Adrien Rabiot, meanwhile, recently returned to regular training action after shaking off a knee injury.
AC Milan has its fair share of concerns ahead of Wednesday's match as head coach Clarence Seedorf will be without suspended midfielders Riccardo Montolivo and Sulley Muntari.
Additionally, Brazil forward Robinho is injured, while Stephan El Shaarawy is still sidelined as well.
To make matters even worse, new signing Keisuke Honda is cup-tied after featuring in the Champions League with CSKA Moscow before the winter break.
For Atletico, young defender Javier Manquillo is out of action after picking up a neck injury in the derby loss versus Real Madrid. Midfielder Tiago Mendes should also miss both legs with knee and wrist complaints.
Left back Felipe Kasmirski is sidelined with a thigh problem and is unlikely to recover in time and goalkeeper Thibaut Courtois is struggling with back spasms. David Villa has returned to training.
The Premier League representative has a number of absentees with Kim Kallstrom, Theo Walcott, Abou Diaby, Thomas Vermaelen and Aaron Ramsey all on the sidelines.
Arsene Wenger will also be without Spanish midfielder Mikel Arteta following his red card against Napoli in the group stages.
Bayern, on the other hand, has very few injury concerns, although star attacker Franck Ribery is sidelined after undergoing surgery on a buttock problem last week, while long-term absentee Holger Badstuber is not fully recovered yet either.
Zenit has no notable selection problems ahead of the match against Borussia Dortmund and head coach Luciano Spalletti has a full squad available for his side's first game after the winter break.
Dortmund will possibly be without a number of regulars as the club's ongoing injury woes continue. Jakub Blaszczykowski is definitely unavailable due to his knee injury, while Mats Hummels, Neven Subotic, Marco Reus, Sven Bender and Ilkay Gundogan are all still struggling as well.
Olympiakos lost star player Kostas Mitroglou to Fulham this winter, but will be pleased with its relatively clean bill of health as only Dimitros Siovas seems unlikely to make the game against United.
Manager David Moyes, meanwhile, will be hopeful that Belgium international Marouane Fellaini recovers in time to feature against the Greek champion, while Nani is expected to miss the match due to a hamstring injury. Phil Jones and Jonny Evans on the other hand could return for United.
Additionally, new signing Juan Mata will have to watch the game from the stands as he's cup-tied having featured for Chelsea in the group stages.
Experienced defender Gokhan Zan is likely to miss Galatasaray's first leg of the round of 16 tie against Chelsea due to injury, while Roberto Mancini will also have to make do without Aydin Yilmaz due to a fractured foot.
Chelsea boss Jose Mourinho will be without new signings Nemanja Matic and Mohamed Salah as both previously played Champions League football this season for Benfica and Basel respectively.
Additionally, Dutch midfielder Marco van Ginkel is not fully match fit yet as he continues his recovery from a knee injury, while Fernando Torres also remains unavailable.
Former Bayern Munich defender Jan Kirchhoff will miss the clash with Real Madrid as he is both cup-tied and injured, with Schalke facing something of an injury crisis.
Benedikt Howedes, Dennis Aogo, Christian Fuchs, Atsuto Achida, Roman Neustadter and Christian Clemens are all fighting fitness problems.
Real Madrid will be without the suspended Sergio Ramos following his red card in the group stages against Galatasaray.
Furthermore, Germany international Sami Khedira is still sidelined with a knee problem and will not feature either.