Left-back Mendy limped off during Saturday’s 5-0 destruction of Crystal Palace, which made Guardiola’s team the outright Premier League leaders.
Fabian Delph and Danilo are both in contention to start if the France international fails to recover in time.
Midfielder Ilkay Gundogan and centre-back Vincent Kompany will definitely miss out, despite being back in training after recent injury problems.
Gundogan sprained his left knee during last Wednesday’s 2-1 Carabao Cup third-round win at West Brom, while Kompany suffered a calf injury playing for Belgium against Gibraltar in a World Cup qualifier at the end of August.
Guardiola said of Mendy: “We are going to give him a test to see if he is able to play.
“Ilkay trained yesterday and so did Vincent, but neither is ready for Tuesday.”
Manchester City have won seven out of eight games in all competitions so far, but Guardiola has warned against complacency.
He said: “It is the seventh time I have played against Shakhtar in my career, once in the Super Cup and three in the Champions League, and every time before I have the same feeling.
“The first time we face in the group stage, my team went to see them and came back saying ‘wow’. My team were really impressed. Fernandinho played and Douglas Costa and they had a lot of Brazilians.
“In Barcelona all the time it was the same. ‘Shakhtar, Ukraine, who cares? Which players play? Nobody knows them.’
“I can assure you they were one of the best teams in terms of playing football. They had five or six Brazilians. Always was so tough for me.”
