Louis van Gaal opens his domestic campaign at Old Trafford but his options in defense are stretched with the absence of Luke Shaw, while Jonny Evans and Rafael are also doubts.
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Van Gaal, who guided the Netherlands to third place at the World Cup this summer, opens his United reign with a fixture at Old Trafford against Garry Monk’s side.
"We can't wait to get going against Swansea and look to put right the wrongs from last year," midfielder Tom Cleverley told United's website. "This club has always been renowned for bouncing back from sticky patches and that's one of the reasons it's so loved around the world."
Swansea claimed its first win at Old Trafford in the FA Cup third round last season and Monk is happy to deflect the attention onto his opposite number.
"All the focus will be on them, which suits us fine," he said. "We'll just go up there and do the best we can. The big clubs attract the most attention — the best players in the world play for these bigger clubs. All the focus is on them and we'll just go about our jobs.
"Everyone is beatable, the best teams in the world are beatable. You always have the chance and we'll be going up there believing we can win the game. We don't fear it — we see it as a challenge."
United has refreshed its squad with the acquisitions of Luke Shaw and Ander Herrera during the summer but Shaw — a 30 million pound signing from Southampton — is sidelined for up to four weeks with a hamstring injury.
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Jonny Evans, Rafael, Antonio Valencia and Danny Welbeck all missed United's final preseason friendly against Valencia on Tuesday and could be injury doubts for Saturday.
Michael Carrick is also absent as he continues to recover from ankle surgery, while star striker Robin van Persie was given an extended break after the World Cup and is still lacking match fitness.
Swansea, meanwhile, has experienced a sizeable turnover in personnel since the end of last season.
Pablo Hernandez, Chico Flores, Ben Davies and Michel Vorm have all left the club, while Michu has moved to Napoli on a season-long loan.
Lukasz Fabianski, Bafetimbi Gomis and Jefferson Montero are all likely to make their debuts against United, and Gylfi Sigurdsson could be in line to kick-start his second stint with the club.
Leon Britton, Marvin Emnes and Jay Fulton are all missing for Swansea with knee injuries.