De Bruyne attempted to play on, but slumped to the ground moments later and then walked off in the 86th minute.
"We are sad for him".
However, the 27-year-old went down holding his knee after a challenge involving on-loan Manchester United ace Timothy Fosu-Mensah.
Guardiola said the Premier League champions were eager to keep Diaz, but added the decision was in the hands of the Spain youth global.
It means De Bruyne will certainly miss next weekend's showdown with Manchester United, while he is a doubt to be available to face Premier League title rivals Chelsea on December 8. We will do absolutely everything to keep him with us - afterwards, he decides.
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Diaz's goals against Fulham were his first for the club and his contract situation has sparked reported interest from Real Madrid. "They know how we tried to help them in the particular way we want to play".
He doubled the lead in the 65th by slotting a shot high into the net from close range after Gabriel Jesus' curling effort came back off the post.
With the cup game squeezed in between two Premier League fixtures in a six-day span, Guardiola took the opportunity to play many of his fringe players.
De Bruyne was given a start, however, and impressed before his injury with his teasing crosses and passes.
"You can not expect a player like we know Kevin is to come back and have the rhythm and the pace and everything".
"It was a hard situation because of the pitch and the conditions and tough physicality but today again he was involved in the offensive and defensive side, in the pace, in the set pieces, the passes and assists".