The Blues tackle Arms Park visitors Montpellier knowing that only a victory will be enough to revive hopes of progressing from Pool Six. But they will go into battle without injured Wales internationals Leigh Halfpenny, Jamie Roberts and Bradley Davies, in addition to regular first-team performers like Tom James, Dan Fish and Michael Paterson.
"Only a fortnight ago, things were looking very positive for us when we were welcoming back some key players," Blues rugby director Phil Davies said. "However, we have been extremely unfortunate to pick up a raft of injuries in the last few weeks."
He added: "It is frustrating that we cannot select from a full-strength squad for these crucial matches, but on a positive note it gives a chance for some of our other players to step up and show what they can do."
The Blues are eight points adrift of group leaders Toulon heading into this weekend's action, while Montpellier could yet challenge their French rivals given that they have home advantage against them next month.
"Montpellier have a formidable reputation in the French league as a very physical team with an extremely strong set-piece," Davies added. "Their scrum is particularly strong this season, having won all 17 of their put-ins so far in both Heineken Cup games, and their six lineout steals is a joint high this season."
Leicester welcome back a batch of England internationals from autumn Test duty when they host Pool Two opponents Treviso.
Manu Tuilagi, Ben and Tom Youngs, Dan Cole and Geoff Parling are all involved at Welford Road, with Parling captaining the side.
Victory for the Tigers, both on Sunday and in next weekend's return fixture, would keep their quarter-final ambitions on course as they head towards a January showdown with Toulouse during the final round of pool action.
Sunday's other Heineken clash is a Pool Five blockbuster in France, where group leaders Clermont Auvergne meet reigning European champions Leinster. Both teams are unbeaten, but Clermont hold a two-point advantage thanks to bonus-point successes against the Scarlets and Exeter.