Graham Potter's men sit at the top of the section on seven points, while their Austrian hosts sit one place and one point worse off in this top-of-the-table showdown.
Match preview
Red Bull Salzburg's ability to compete with the European big guns while nurturing some of the finest young talent that Europe has to offer is admirable, but failure to convert draws into wins has been the downfall for the Austrian champions, who have lost their grip on top spot.
Matthias Jaissle's side are still unbeaten in the section - no mean feat given the calibre of opponents that they have pitted their wits against - but they could not hang on to a one-goal lead against Dinamo Zagreb on matchday four, as Nicolas Seiwald's opener was cancelled out by Robert Ljubicic.
Nevertheless, Salzburg's fate remains in their own hands ahead of the penultimate round of matches, and victory would be enough to guarantee them a place in the last 16 if AC Milan and Dinamo Zagreb's encounter ends all square, but they could also drop out of the top two if results do not go their way.
The Austrian powerhouses have remarkably gone unbeaten in their last 16 matches in all competitions this term but were held to a goalless stalemate by Sturm Graz in league action at the weekend, and only two of their last nine Champions League matches have actually ended in victory.
On the flip side, not since December 2020 have Jaissle's men lost a home game in Europe's premier tournament - with Milan, Sevilla, Bayern Munich and Lille among the clubs to have failed to win at the Red Bull Arena since - and Chelsea also know a thing or two about stalemates.
When taking a quick glance at Chelsea's Champions League points tally, one would assume that the Blues' pair of victories had come against Salzburg and Dinamo Zagreb, but the Potter magic has been in full flow during back-to-back meetings with Italian champions AC Milan.
Seeing off the Rossoneri by an aggregate scoreline of 5-0 has reignited Chelsea's charge for the Champions League knockout rounds, and the West London club need only come away from the Red Bull Arena with another three points to their name to guarantee a top-two finish.
Top spot will not be guaranteed just yet, with Dinamo Zagreb still capable of throwing a spanner in the works, and Potter's men have played out successive stalemates with Brentford and Manchester United heading into this game, with Jorginho's penalty against the latter being wiped out by a last-gasp Casemiro header.
The Brazilian's effort may have denied Chelsea a sixth straight clean sheet, but Potter is unbeaten in eight matches domestically and continentally since taking over at Stamford Bridge, and the Blues travel to Austria in the knowledge that Salzburg have never beaten an English team in seven previous attempts.
Potter's first game in charge of the 2021 Champions League holders ended in a 1-1 draw with Salzburg at Stamford Bridge, as Noah Okafor cancelled out Raheem Sterling's opener, and the hosts are battling both history and a hefty injury list in their bid to upset the Group E apple cart.
Red Bull Salzburg Champions League form:
D
D
W
D
Red Bull Salzburg form (all competitions):
W
L
D
D
W
D
Chelsea Champions League form:
L
D
W
W
Chelsea form (all competitions):
W
W
W
W
D
D
Team News
Salzburg have an unenviable list of absentees to deal with for the visit of Chelsea, as Justin Omoregie (hamstring), Fernando (thigh), Ousmane Diakite (ACL), Nicolas Capaldo (knee), Sekou Koita (thigh) and Dijon Kameri (shoulder) are all among the players expected to miss out.
Key midfielder Luka Sucic has also emerged as a fresh concern with an adductor injury after being forced to pull out of the draw with Sturm Graz at the last minute, but 36-year-old captain Andreas Ulmer is hopeful that he will come back from a knock to line up from the off.
Strahinja Pavlovic was sent off at the weekend but will hold his place in the backline here, and Benjamin Sesko will be vying to return to the attacking line in place of Junior Adamu, with Noah Okafor aiming to build on the three Champions League goals that he has already struck this term.
Chelsea's treatment room is not as brimming, but Wesley Fofana and Reece James remain out of contention with their knee injuries, and N'Golo Kante will take a few months to recuperate from hamstring surgery.
Kalidou Koulibaly was a notable absentee from the draw with Man United, and Potter subsequently revealed that the Senegal defender experienced knee pain after the Brentford stalemate, and he will need assessing here. Meanwhile, Mateo Kovacic's failure to start on Saturday was down to careful management over his own knee issue.
Potter had no room for sentiment against Man United, taking off ex-Brighton & Hove Albion colleague Marc Cucurella in an early switch to a back four, and the Blues boss could make such a change from the first whistle here if Koulibaly is indeed ruled out.
Red Bull Salzburg possible starting lineup:
Kohn; Dedic, Solet, Pavlovic, Ulmer; Kjaergaard, Gourna-Douath, Seiwald; Sucic; Okafor, Sesko
Chelsea possible starting lineup:
Kepa; Azpilicueta, Chalobah, Silva, Chilwell; Gallagher, Jorginho, Loftus-Cheek; Mount, Havertz, Sterling
We say: Red Bull Salzburg 1-2 Chelsea
In spite of their lengthy injury list, Salzburg are rarely kept at bay in the Champions League, and the rejuvenated Kepa Arrizabalaga will need to be on top form to keep out Jaissle's menacing attacking starlets.
The Blues were second best for the majority of their battle with Man United, but Potter's side should still take advantage of Salzburg's depleted squad to seal their place in the last 16.
Fiorentina 
Udinese 
Benfica 
Estoril 
Inter 
Como 
Manchester City 
Everton 
Chelsea 
Fulham 
Nottingham Forest 
Tottenham 
Celtic 
Motherwell 
Wolverhampton 
Manchester Utd 
ST Mirren 
Rangers 
Sampdoria 
Carrarese 
Liverpool 
Leicester 
Arsenal 
Ipswich 
Cagliari 
Lazio 
Atalanta 
FC Porto 
Boavista 
Torino 
Napoli 
Venezia 
ST Johnstone 
Juventus 
West Ham 
Pisa 
AC Milan 
Roma 
Sporting CP 
Newcastle 
Brentford