The Tottenham Hotspur loanee missed his side's Champions League loss to Galatasaray with a tight hamstring, where Sofyan Amrabat struggled in an unfamiliar role as his team slumped to a 3-2 beating.
Man United are reportedly deciding whether fielding Reguilon this weekend is worth the risk, and Erik ten Hag should provide an update later this week, but Luke Shaw (muscle), Tyrell Malacia (knee) and Lisandro Martinez (foot) are definitely out.
Unless Reguilon is thrown back into the deep end, Amrabat will hold his place in the backline, where Jonny Evans might have a case to come in for Victor Lindelof after the Northern Irishman's impressive feats against Burnley.
Despite another high-profile mistake in midweek, Andre Onana will not lose possession of the gloves just yet, while Diogo Dalot and Raphael Varane are surefire starters in front of the Cameroonian.
Onana's poor pass to Dries Mertens in midweek forced Casemiro into giving away a penalty - and receiving a red card for his troubles - but the Brazilian is fine to take part this weekend and could join Mason Mount in an untouched engine room.
Bruno Fernandes will wear the armband from the number 10 spot as ever, while Antony came off the bench against Galatasaray after being reintegrated into the team amid allegations of domestic abuse, which he firmly denies.
The Brazilian could now return to the final third alongside Rasmus Hojlund and Marcus Rashford, despite claims that the latter's spot may be in jeopardy on account of an underwhelming start to the season.
Manchester United possible starting lineup: Onana; Dalot, Varane, Evans, Amrabat; Casemiro, Mount; Antony, Fernandes, Rashford; Hojlund