The Algerian worldwide is widely viewed as one of the top attacking left-backs in the world and has no intention of signing a new deal at San Paolo, where City will travel to on November 1 having been paired with Maurizio Sarri's side in the Champions League group stage.
Mendy, who has made a positive impression since his summer move from Monaco, attended the Shakhtar game on crutches and Guardiola admits he could seek a short-term replacement if fears of a lengthy absence are confirmed.
After tests in Manchester at the start of the week, the 23-year-old travelled to Spain to see a specialist doctor and further examinations of the knee on Thursday confirmed the extent of the injury.
City have not yet revealed how long Mendy will be out of action, but such an issue leaves his participation over the remainder of the campaign in doubt.
Amiens stadium barrier collapses, 29 remain in hospital
Bad scenes in Amiens , where a barrier collapsed under weight of Lille fans celebrating a goal. She said: "Our emotion and solidarity is with the Lille fans".
The last high-profile footballer to suffer an ACL injury was Manchester United striker Zlatan Ibrahimovic.
To make matters worse for Pep Guardiola and City, star striker Sergio Aguero has reportedly been involved in a vehicle crash after attending a concert in Holland. "He didn't make one training session with us since a month ago".
No Mendy and now no Aguero?
City boss Pep Guardiola praised Delph and reckons Gareth Southgate can benefit from including the midfielder in his squad.