The Guinness Premiership champions need a bonus-point victory to keep alive quarter-final prospects that were seriously weakened by successive away losses against the Ospreys, and then Stade in Paris last Sunday.
Sharks rugby director Philippe Saint-Andre said: "This is a must-win game for us. We need to win, and we need to score four or more tries, it is as simple as that.
"The players put in a lot of effort last week, and we almost gained a valuable bonus point."
Sale plan late fitness tests for centre Mark Taylor and Juan Martin Fernandez-Lobbe, but England wing Mark Cueto and hooker Sebastien Bruno are definite non-starters at Edgeley Park through injury.
Sharks number eight Sebastien Chabal, who was Sale's outstanding player at Parc des Princes, added: "We made too many little mistakes, and the Stade wings punished us.
"We know we have got it all to do now, and it looks like what the Ospreys did to us at the Liberty Stadium in October (Sale suffered an injury-time defeat) caused the damage."
While Sale prepare for a make-or-break encounter, Pool Two outsiders Gloucester must follow up last Saturday's home victory over Edinburgh with a repeat result in the Murrayfield return, or effectively face elimination.
Flanker Andy Hazell makes his first Gloucester appearance since mid-October after recovering from a shoulder problem, while prop Nick Wood starts instead of Patrice Collazo, who is serving a one-week suspension.
Behind the scrum, half-backs Ryan Lamb and Rory Lawson gain starts, with full-back Iain Balshaw replacing Olly Morgan.
Gloucester head coach Dean Ryan said: "I think I am right in saying that Edinburgh have beaten Wasps at home in this competition in the past, and they have already beaten Leinster this season, so we are under no illusions about the intensity of this challenge.
"Our squad is learning about the pressures involved in this tournament - of different opposition, new referees and venues - and I think we have taken on board some of the lessons we learnt in our first two games against Leinster and Agen.
"We were very conscious that we didn't want Europe to become a series of lessons with nothing attached to the games, and we have ensured we are still alive in the pool, which is all we can do."