The French international limped off in City's 5-0 thrashing of Premier League whipping boys Crystal Palace on Saturday.
That win kep City top of the Premier League table, but it came at a cost, with Mendy now a doubt for the visit of Shakhtar.
Guardiola could opt to field either Fabian Delph or Danilo in Mendy's place should the Frenchman not make it.
There is some good news for City fans, with midfielder Ilkay Gundogan and defender Vincent Kompany both back in training, but the game on Tuesday will come too soon for both of them.
Speaking of Mendy ahead of the game Guardiola said: "We are going to give him a test to see if he is able to play. Ilkay (Gundogan) trained yesterday and so did Vincent (Kompany), but neither is ready for Tuesday."
PEP: We are going to test and see if @benmendy23 is able to play.
— Manchester City (@ManCity) September 25, 2017
PEP: @IlkayGuendogan yesterday trained for part. He just played with the ball. @VincentKompany is not ready for tomorrow.
— Manchester City (@ManCity) September 25, 2017