Jose Mourinho's side have endured a difficult pre-season period, full of fitness and transfer frustrations, but have won their opening game in each of the last three seasons.
The Red Devils find themselves in the unusual position of being overlooked as title contenders. They have a 19-point gap to make up on champions Manchester City from last term and there is a lot more optimism of a challenge across the border at Liverpool than there is at United.
Mourinho's last two jobs - at Real Madrid and Chelsea - have ended turbulently during his third year in charge and there are signs that history could repeat itself.
The Portuguese appears to have alienated Paul Pogba and Anthony Martial, two of his most exciting offensive players, to the extent that both have been angling for a move away from Manchester this summer, according to reports.
United's pre-season results and performances have been underwhelming and Mourinho has publicly belittled the young players who made up their US touring party in the absence of those World Cup stars who have enjoyed an extended break.
One positive from United's summer is the form of Alexis Sanchez, who was far from his glittering best upon joining from Arsenal last January. With several of United's star names likely to miss the start of the campaign there will be pressure on the Chilean to hit the ground running.
However, Sanchez had admitted his disappointment with United's summer business and the lack of quality arrivals. Defensive midfielder Fred from Shakhtar Donetsk is the club's only major acquisition, along with young defender Diogo Dalot and third-choice goalkeeper Lee Grant.
The Red Devils were linked with a host of centre-backs on deadline day but moves for Atletico Madrid's Diego Godin, Tottenham Hotspur's Toby Alderweireld or Leicester City's own Harry Maguire never materialised, with suggestions that Mourinho and the board were at odds over the preferred target.
There seems to be the potential for United to implode in the same manner that Chelsea did in Mourinho's second spell at Stamford Bridge, but a few good results to start the campaign might get them back on track.
Pre-season form: LWLDDD
Claude Puel survived the summer but will know that his position may not be secure for long unless he can turn around the form in which the Foxes finished last season.
After a honeymoon period of one defeat in his first nine matches upon arriving last October, the Frenchman oversaw just five wins across the next 21 league games and Leicester only narrowly hung on to a top-half finish.
The club's owners have been spoilt by the miracle title win of 2015-16 as they have not since gone through a season without making a managerial sacking, and they may not waste much time continuing that trend unless Puel can show improvements immediately.
Riyad Mahrez finally got his move to Man City and leaves a huge creative and goalscoring void, having contributed a combined 60 goals and assists across the last three seasons. Leicester will be hoping that lightning strikes twice having brought in another Algerian winger - Rachid Ghezzal - from AS Monaco as his direct replacement.
Norwich City youngster James Maddison has also arrived but most of Leicester's recruitment focus this summer was on shoring up a defence which conceded 60 goals last term - the fifth worst record in the division.
Portugal international Ricardo Pereira should make the right-back spot his own after joining from Porto, while Jonny Evans is a very astute signing as partner to Maguire, for whom the Foxes reportedly rejected two offers from Friday's opponents.
The England World Cup hero, along with Jamie Vardy, will be key to Leicester's hopes of launching a European bid, but they will need the likes of Demarai Gray and Kelechi Iheanacho to step up if they are to keep pace.
Pre-season form: WDLDW
United have an extensive injury list including midfielders Nemanja Matic and Ander Herrera as well as captain Antonio Valencia. Eric Bailly is another doubt so Victor Lindelof is on standby to partner Chris Smalling in a defence which could also include Matteo Darmian and Luke Shaw, despite their disposability to Mourinho.
The World Cup contingent of Ashley Young, Marouane Fellaini, Jesse Lingard, Romelu Lukaku and Pogba are unlikely to feature. Marcus Rashford may be rushed back to play wide left due to Mourinho's shortage of options, which is not helped by Martial's uncertain future, with Sanchez expected to start through the middle.
Fred will make his debut in a three-man midfield designed to get the best out of Pogba on his return, and alongside him Andreas Pereira finally has the chance to prove himself after a decent loan spell at Valencia last term.
Puel could hand debuts to Ricardo Pereira and Maddison, and will make a late call on Evans who is nursing a muscle strain. Maguire is short of match fitness but is on hand to deputise with 21-year-old signing Filip Benkovic unlikely to be thrown in at the deep end. Otherwise, he and Vardy will probably start on the bench.
Man Utd possible starting lineup:
De Gea; Darmian, Bailly, Smalling, Shaw; Fred, Pereira, McTominay; Mata, Rashford, Sanchez
Leicester possible starting lineup:
Schmeichel; Pereira, Morgan, Evans, Chilwell; Ndidi, Iborra; Albrighton, Maddison, Gray; Iheanacho
Head To Head
United are unbeaten in eight matches against the Foxes since losing a 5-3 classic at the King Power Stadium in Leicester's first season back in the top flight in 2014. They also faced them in August last season, when goals from Rashford and Fellaini earned Mourinho's men a 2-0 win.
The Red Devils have only lost at home once to the East Midlands outfit in the Premier League era - back in 1998 when Tony Cottee scored the winning goal.
We say: Man Utd 1-1 Leicester
That prospective United lineup must be as uninspiring as any they have fielded for the first game of a Premier League season. Sanchez is the sole player of real quality and it is difficult to see where his service is going to come from as that midfield lacks proven creativity.
Although their recent record against the Red Devils is not great, Leicester do fare quite well against top-six opposition because of their counter-attacking strengths and they will take advantage of United's missing men to take a valuable opening-day point away from Old Trafford.