Shawcross, who recently committed his long-term future to Stoke by signing a new four-year deal, is struggling with a back problem and his absence for the visit of his former club will be a blow.
“Unfortunately Ryan has pulled up in training and is likely to miss certainly the weekend –hopefully it won't be any longer,” Hughes said at a press conference on Friday.
“He's got an issue with his back. It's not what he's had before in terms of disc injuries, it's ligaments around the back and we have to wait for him to settle down.”
The absence of Shawcross, 29, who is closing in on his 400th Stoke appearance, could mean a debut for Austrian international Kevin Wimmer, signed for £18million from Tottenham this summer.
The fitness of another summer signing is also up in the air: winger Maxim Choupo-Moting strained a hamstring while on international duty with Cameroon, and many not feature at the Britannia Stadium.
But a third ex-United man, Darren Fletcher, is hopeful of shaking off a knee injury in time to face his former club. The 33-year-old defensive midfielder – who missed Scotland's World Cup qualifiers against Lithuania and Malta – is now back in training.
Hughes also took time to praise Manchester United’s start this season. Mourinho's side have won all three of their opening league games, scoring 10 goals without reply. “Of all the teams they are clearly at the top of the pile,” Hughes said.
“Their performances and the way they've gone about their business has been impressive. The make-up of the United squad is very strong and they're playing in a way that their fans will take to and enjoy. They expect teams to attack with power and pace and ability.”
But he also emphasized that Stoke are out to win. “It's very early days. Hopefully there are still things for us to exploit,” he added.
“These games are huge for us and we always enjoy them. We hope we can get a similar result that we did against Arsenal.”
Hughes is unbeaten in four home league meetings against his former club during his time in charge at the Britannia. The Potters are currently 11th, with a win, a draw and a defeat from their opening three games.
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