The manor of that defeat - an 83rd minute penalty putting Gloucester ahead - will give the Saints extra motivation against Sale on Friday, and they are rightly favourites to claim the competition two points.
Jim Mallinder's men have been handed the biggest handicap of the weekend and it's easy to see why when you look at the star-studded pack which includes the likes of Alex Corbisiero and Courtney Lawes.
Sale, on the other hand, have been struck with a few injuries, meaning their odds move from 8/1 to 12/1 to win the game outright.
On Saturday, London Irish face another tough task as they tackle a Bath side looking for redemption after losing to Saracens last week.
The home side also receive a double-figured handicap, based largely on a seven-point victory over Champions Leicester in their only other game at the Rec this season.
Bath were comfortable victors in this fixture last year and early indications suggest that the exiles will struggle again in 2013/14.
Despite not winning a game so far this season, London Wasps still find themselves with three competition points and are favourites to add to that as they take on Worcester Warriors.
They have a nine point handicap to their name this week and, with Worcester lying at the foot of the table, signs are they will struggle at Adams Park once again.
The Warriors' last away win did come at this weekend's venue, however, and they are 10/3 to duplicate their success from New Year's Day 2012.
Nothing to compare
It's expected to be a lot tighter at the Twickenham Stoop however, as Harlequins attempt to be the first side to take points from last year's table-toppers.
Both sides have started at scratch, yet the Quins did begin the week with a slight handicap in the betting.
This market could move again prior to kick off given Saracens perfect start to the season and knowing they have won five of their last six visits to the Stoop.
David Strettle has proved the most popular bet in the try scorer market after scoring four tries already this season.
Leicester Tigers were the last side to inflict defeat on Exeter at Sandy Park and are odds-on to do it again on Sunday afternoon.
They are not huge favourites though at 5/6 and only have a -3 handicap to overcome.
The short handicap may surprise a few - the Tigers have won two of three games by over 15 points this season - but they edged the Chiefs out by just three points in this fixture this year.
Despite a shock win at Sale in Round Two, Newcastle still find themselves near the foot of the table and, this week, they take on Gloucester who are fresh from a last-minute victory over much-fancied Northampton Saints.
The +6 handicap for Newcastle would have been lower had this been the first game of the new campaign but two heavy defeats for the Falcons already this term has meant Gloucester will start the match odds-on at 1/3.