After the disappointment of Heineken Cup defeat to Leinster last week, Harlequins' hopes of reaching the Guinness Premiership semi-finals were dealt a blow with a 28-6 defeat to Sale on Friday.
Sebastien Chabal marked his return to action with a crucial second-half try. The France international, who will depart Edgeley Park at the end of the season, had missed Sale's previous six outings due to injury and international commitments but he found the space to burrow over shortly after the restart.
Replacement Rudi Keil added a third score for the hosts in the 63rd minute to add to a first-half penalty try before replacement Richard Wigglesworth added a fourth score which confirmed a victory that booked Sale's place in next season's Heineken Cup.
Kingsley Jones' men must now beat Northampton at home next Saturday to stand any chance of finishing in the top four after losing five of their previous six Premiership outings prior to this encounter.
Sale had the first opportunity to open the scoring inside the second minute but spurned it when fly-half Charlie Hodgson screwed a penalty wide of the posts from distance.
Four minutes later, Waisea Luveniyali missed a penalty for the visitors but it was Harlequins who began to gain the ascendancy following the sin-binning of Sale wing Oriol Ripol in the 13th minute for persistent infringement.
They led when Luveniyali converted a 17th-minute penalty and threatened to run right through Sale in a series of promising moves.
Sale offered little going forward but almost managed to engineer an opening down the left flank when Andy Tuilagi found Mathew Tait bursting forward at pace.
Tait's neat short offload was collected by David Doherty but his progress was checked and the momentum remained largely in Harlequins' favour.
Having replaced David Strettle with Danny Care midway through the half, they wasted the chance to go 6-0 up soon after when Andy Gomarsall's errant penalty attempt sailed wide.
The game began to warm up as the first half wore on and in the 34th minute Harlequins' Mike Ross was sin-binned for persistent infringement following a series of broken scrums.
A penalty try was eventually awarded to Sale in the 36th minute and Luveniyali failed to reduce the arrears on the stroke of half-time when he sent a penalty wide of the posts.
The momentum remained with Sale after the break and within two minutes of the restart they claimed their second try when Chabal burrowed his way over from close range.
Hodgson converted and Sale continued to press forward their advantage, despite Gomarsall's penalty on the hour mark keeping the visitors in contention.
They were rewarded in the 63rd minute when Keil collected possession and showed impressive pace to burst clear of a stunned Harlequins rearguard to touch down.
Hodgson again added the extras to put Sale 21-6 ahead and then Wigglesworth added a fourth score when he took Ripol's pass and touched down in the closing stages for a try which Hodgson again converted.
Tries: Penalty try, Chabal, Keil, Wigglesworth
Cons: Hodgson 4
Pens: Leveniyali, Gomarsall
Yellow cards: Ripol (Sale, 13), Ross (Harlequins, 38)
Sale: 15 Nick Macleod, 14 David Doherty, 13 Mathew Tait, 12 Andy Tuiagi, 11 Oriol Ripol, 10 Charlie Hodgson, 9 Dwayne Peel, 8 JM Fernandez Lobbe (c), 7 Neil Briggs, 6 Jason White, 5 Dean Schofield, 4 Sebastien Chabal, 3 Eifion Roberts, 2 Sebastien Bruno, 1 Andrew Sheridan,
Replacements: 16 Stuart Turner, 17 Lionel Faure, 18 Chris Jones, 19 David Tait, 20 Richard Wigglesworth, 21 Rudi Keil, 22 Selorm Kuadey
Harlequins: 15 Tom Williams, 14 David Strettle, 13 Gonzalo Tiesi, 12 De Wet Barry, 11 Ugo Monye, 10 Waisea Luveniyali, 9 Andy Gomarsall, 8 Nick Easter, 7 Will Skinner (c), 6 Chris Robshaw, 5 George Robson, 4 James Percival, 3 Mike Ross, 2 Gary Botha, 1 Ceri Jones.
Replacements: 16 Tani Fuga, 17 Mark Lambert, 18 Jim Evans, 19 Tom Guest, 20 Danny Care, 21 Seb Stegman, 22 Jordan Turner-Hall.
Referee: Wayne Barnes
Touch judges: Alan Hughes, Paul Emerson
Assessor: Brian Leigh
Television match official: Andrew Turner