Gloucester have experienced rare joy with two European Challenge Cup wins over the last fortnight and will aim to add to Sale's recent woes on Sunday afternoon (KO, 15:00).
The Sharks have lost their last four to both fall out of the Premiership play-off places and be eliminated from the European Champions Cup, with a round of 16 tie against Ospreys in the Challenge Cup their next continental assignment.
A win in Wales and a matching result for Gloucester against Castres will see these two meet in the quarter-finals after the Challenge Cup's somewhat convoluted seeding system put the duo in the same bracket.
That hypothetical fixture will come after the Six Nations, with the Premiership set for a break during the Championship, meaning a defeat for either side on Sunday will hurt even more.
Sale will have two months to stew, while the Cherry & Whites have some consolation in the chance to bounce back in the latter stages of the Premiership Rugby Cup.
With their respective campaigns at a crossroads, coaches George Skivington and Alex Sanderson will see Sunday's match as potentially season-defining.
Gloucester have made four changes. Kirill Gotovtsev is in at prop for Fraser Balmain and skipper Lewis Ludlow is restored to the back row.
Adam Hastings' injury provides recent arrival Charlie Atkinson with a chance to make his debut following his switch from Leicester. He will start in the number 10 shirt, while the other alteration sees Alex Hearle selected on the right wing.
Sale are boosted by the returns of forwards Ernst van Rhyn, Dan du Preez, Si McIntyre and Cobus Wiese, while Joe Carpenter starts at full-back, with Telusa Veainu switching to the wing.
That change is necessitated by Tom Roebuck's England call-up alongside Luke Cowan-Dickie, Ben Curry and George Ford, while Jonny Hill, Tom Curry and Manu Tuilagi are all injured.
Gloucester are 4/6 to win for the first time in the league since 20th October, with Sale 11/8 and the tie 18/1.
The handicap on Gloucester is -3, available at 10/11, while the pair's nine meetings prior to Sale's 14-point victory in November's reverse game - a 24-10 success - were decided by 10 or fewer.
Gloucester are 17/10 to succeed by 1-12 points included, with Sale 23/10 in the same market.
Sale to win @ 11/8
Gloucester will be buoyed by their Challenge Cup victories over Edinburgh and Castres. However, they also won both of their continental outings in December, only to lose three in a row domestically and that inability to back up results must be playing on the Cherry & Whites' minds.
Skivington's side have a few weeks off before facing Exeter in the Premiership Rugby Cup and, with relegation unlikely, they may already be thinking about that competition as they aim to salvage their season.
They may also feel they are playing Sale at the perfect time, but the Sharks won last season's trip to Kingsholm and that success in November means they have won the last four meetings.
Sanderson may be framing this game as Sale's 'last dance' before the Six Nations, demanding his players give their all to boost confidence heading into the break before returning in March.
Despite their enforced absences, the Sharks still possess plenty of quality and can sneak the victory, while more positive punters might take them to triumph by 1-12 points inclusive, as was the case in last season's 25-22 success.
You can read all our Rugby Union Betting Tips over at our dedicated Insights hub.