Kompany has not turned out for Pep Guardiola’s side since the 2-1 victory over Liverpool in early January after suffering a muscle injury.
Mendy, meanwhile, is recovering from a meniscus knee injury. The left-back made a brief return last month but has not been seen since.
Guardiola expects the Premier League champions will “suffer” against League Two outfit Newport, who have already knocked Leicester City and Middlesbrough out of the cup this season.
“What they do, they do it really well. We’ve watched as many games as possible to understand what they do. We respect them a lot,” he said.
“We are going to suffer because they are taller and stronger than us. In some areas, they are better than us.
“We have to try to bring our game in the way we are stronger than them. Which team controls these areas, or brings their own game, in that moment will have the advantage to go through.”
Newport manager Michael Flynn is unable to call upon midfielder Andrew Crofts but otherwise has a clean bill of health. Harry McKirdy, a loan signing from Aston Villa, could feature.
“Joss Labadie is fine, Mark O’Brien is fine. Harry McKirdy is available, he can come in to the team,” Flynn said.
“Harry is definitely registered – he might be involved and he might not be. It all depends whether I feel he’s ready or not.
“He gives us another option. Harry is a big Chelsea fan and I think he went to the game on Sunday [City’s 6-0 defeat of Chelsea]. He’s definitely got a score to settle.”
Newport County: Day; Poole, Demetriou, O’Brien; Willmott, Bakinson, Labadie, Bennett, Butler; Amond, Matt.
Manchester City: Ederson; Danilo, Stones, Otamendi, Delph; Foden, Gundogan, D. Silva; Mahrez, Jesus, Sané.
Referee: A Marriner (West Midlands)
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