Joe Allen will miss Stoke's trip to Manchester City due to the concussion he suffered while on international duty with Wales.
The 27-year-old midfielder took a blow to the head having been caught between David Meyler and James McClean during the Republic of Ireland's victory in Cardiff on Monday that dashed Wales' World Cup hopes.
Hughes revealed Allen had little recollection of the incident and would be missing at the Etihad Stadium because he was not far enough along in the concussion protocol process.
"Joe's not great; we've given him a couple of days just to stay at home," Hughes said.
"He came in yesterday (Thursday), felt a lot better, but I think the reality is he's unlikely to be available unfortunately.
"Clearly concussion's a thing you can't take any risk with, we've got to follow the protocol. Hopefully he'll start to show some improvement and be ready to come back and train at some point next week. He's not going to be available this week.
"He was allowed home but he had a bang to the head. He found it difficult to remember the incident itself - that tells you where he's at in terms of the severity of it.
"We've got to be very careful. We're being guided by the medical people here. At the moment he's not in position to return to training."
Allen's withdrawal 37 minutes into the World Cup qualifier proved crucial as a Wales side already missing Gareth Bale failed to get the victory they needed to secure a play-off spot.
Welsh boss Chris Coleman had hinted that the Republic may have specifically targeted Allen for some rough treatment, yet Hughes is unaware of such antics while he has played for Stoke.
"I can't say I've seen that, t hat's a surprising statement," Hughes added.
"I suppose you could argue it might be a realistic statement because he's a good player and sometimes teams go out to stop your better players, the players that have an influence.
"Certainly Joe for Wales and for us is very influential. I can understand it to a certain extent. From my own experience, I haven't witnessed that."
Hughes also expects to once again be without captain Ryan Shawcross (back) and fellow defender Bruno Martins Indi (groin) when he takes his team to Pep Guardiola's league leaders.
City have won their last two Premier League home games 5-0 and Hughes has seen an improvement in the side they drew 0-0 with at the Etihad Stadium back in March.
"As good as they were last year they still felt they needed to go into market and spend Â£200m to address a few areas of the team," Hughes noted.
"That's the resources they have and they use them very, very well. They look a lot stronger this year certainly than they were last year. It's a big test for us but it's not one we're not afraid of."