Mendy missed City's surprise 2-1 defeat by Olympique Lyonnais in the Champions League on Wednesday and was also sidelined for the victory over Fulham last weekend.
"He is injured. I don't know (how long he'll be out). He has a little problem in his ankle, his foot," Guardiola said.
It was later confirmed that Mendy has damaged his fifth metatarsal, although how badly was not known.
City, who are also without Kevin de Bruyne (knee), will be anxious to get back to winning ways after the hiccup against Lyon and Guardiola is expecting a physical challenge against Neil Warnock's promoted Cardiff side.
"Premier League is physical. Not just Cardiff. I realised that when I arrived, " Guardiola said. "Cardiff has a way to play and we have to adapt."
Guardiola played down any suggestion that the early-season demands on his players, most of whom played at the World Cup, had contributed to the Champions League setback.
"It's always difficult. Last season we did almost everything well," he said. "We can't forget what we've done.
"You have to be able to handle it. Most went to the World Cup, most went to the international break. It is what it is."
Earlier in the day City confirmed that Argentine striker Sergio Aguero had extended his contract until 2021.
"I didn't convince him, he decided for himself," Guardiola said. "Thank you so much (to him) for that. He's one of the players who shows his commitment to the club every day."
Third-placed City's most recent Premier League trip to Cardiff came in 2013 when they lost 3-2.
Cardiff have yet to win in their five games this season and have managed only three goals, leaving Warnock with a predicament over whether to attack or sit deep.
"It's a difficult thing from a manager's point of view, do you try and shut up shop because the chances are you're going to get beat anyhow," Warnock said.
"I want them to try and show they can put up a good game against them without just having everyone at the back and defending for our lives all the game.
"(City) are a unique team. I know Liverpool and Chelsea are good, I still think this is the team that have got everything in their locker so it is a real test for you as a team and staff."
(Reporting by Martyn Herman; Editing by Toby Davis)
