The Belgian was taken off for Phil Foden after 58 minutes and immediately headed for the dressing room because of his unhappiness at the decision, according to The Times' Paul Hirst.
In his pre-match press conference before facing Wolverhampton Wanderers in the Premier League on Monday night, Guardiola said: "I didn't speak with him that one time, so I cannot say what he thinks because I don't know. If he has a problem, he knows where I am, so I don't know, really."
De Bruyne had opened the scoring in the one-sided Carabao Cup semi-final first-leg win after just five minutes:
"Oh Kevin De Bruyne"— Sky Sports Football (@SkyFootball) January 9, 2019
It didn't take long.. #MCFC lead thanks to a fifth minute header from the Belgian.
📺 Watch live on Sky Sports Football or follow here: https://t.co/LvgqdiFIng pic.twitter.com/27sPSTrz9Q
It was only De Bruyne's 11th appearance of the season, as he has been out of action for much of the campaign with a knee ligament injury.
As such, it's understandable he may have wanted to remain on the pitch as he works his way back to full fitness, particularly with City not playing again until Monday.
Hirst felt Guardiola might have been pleased to see his reaction to the decision:
This a consequence of De Bruyne’s competitive nature and desire for minutes. Imagine Pep happy that one of his stars is so driven to get back to his best again after two knee injuries in the space of a few months. https://t.co/A5qW8GDAZD— Paul Hirst (@hirstclass) January 10, 2019
The Belgian will be desperate to get back to his best, particularly with City trailing Liverpool in the Premier League title race.
The Sky Blues closed the gap to four points when they beat the Reds on January 3, but they're back to being seven behind at least until they play Wolves, with Liverpool having beaten Brighton & Hove Albion 1-0 on Saturday.
Having De Bruyne back in the team is a welcome boost for City as they look to chase down Liverpool, as he's one of their most influential players.
Last season, he notched 12 goals and 21 assists in all competitions as City won the Premier League title and the Carabao Cup, as well as reaching the quarter-finals of UEFA Champions League.
His creativity is exceptional, as sports scientist and coach Simon Brundish demonstrated:
It's important Guardiola keep him happy, but equally, it may not hurt if the playmaker feels he has a point to prove, as City can ill afford any slip-ups for the rest of the season.
If the Sky Blues do manage to overhaul Liverpool and defend their title, De Bruyne will likely have been vital to their efforts.