Reds seeking rapid redemption at Wigan
For the last two seasons they have won only one of their opening four league matches - and still ended up winning the Premier League.
After crashing to a shock 1-0 defeat at promoted Burnley on Wednesday night, manager Alex Ferguson will not want another setback at Wigan on Saturday - especially as United have won all eight league matches between the two clubs since their Lancashire rivals were promoted to the Premier League in 2005-06.
Ferguson took a philosophical view of United's first defeat to a newly-promoted side for four years - a run of 17 straight wins - after Robbie Blake's stunning volley gave Burnley victory in their first top flight match for 33 years at Turf Moor.
"It is a bad blow to us. I know everyone will say we are never good at the start of the season, we usually take our time and by October we start to get going, but nonetheless we shouldn't be losing these games."
United have been suffering from a spate of injuries, which has ruled out first choice goalkeeper Edwin Van der Sar as well as central defenders Rio Ferdinand and Nemanja Vidic, but the defeat to Burnley, who host Everton on Sunday, was a big upset.
Wigan will also be looking to bounce back with an immediate victory after losing 1-0 at home to promoted Wolverhampton Wanderers on Tuesday night.
New coach Roberto Martinez was critical of their performance against Wolves, especially after they made a good start to the season with a 2-0 win at Aston Villa last Saturday.
"We were sloppy, we didn't have energy and we couldn't get hold of the game and Wolves took advantage," he said.
Unusually, at any stage of the season, the top three in the embryonic league table are London clubs with Tottenham Hotspur leading Chelsea on goal difference after both started with two wins.
Arsenal are third, heading up a pack of teams on three points, having won their solitary game 6-1 at Everton.
Spurs got their biggest away win for 11 years on Wednesday when they demolished Hull City 5-1 with England striker Jermaine Defoe scoring a hat-trick. That followed up their impressive 2-1 opening day win against Liverpool.
On Sunday, they make the short trip to West Ham United with the praises of Hull manager Phil Brown ringing in their ears.
"From a neutral's point of view you would have to say you have just seen a top four team out there," he said.
"They gave us a real lesson and we were never close to them," he added.
Tottenham's main concern ahead of Sunday's match is a knee injury which forced goalkeeper Heurelho Gomes off after just 16 minutes at Hull.
Chelsea play neighbours Fulham on Sunday and, despite Fulham's improvement under coach Roy Hodgson, start as strong favourites, especially after a superb display in their 3-1 win at Sunderland on Tuesday.
Arsenal, who beat Celtic 2-0 in their Champions League qualifier on Tuesday, could be in for another