The Belgian midfielder returned to the game as a substitute for Watford on Saturday but was announced on Tuesday for the Champions League game in Leipzig, City's final Group A installation.
The 30-year-old player suffered a leg tendon injury at Euro 2020 that prevented him from starting a game in the Premier League until the end of September, but he was only just beginning to find his structure when he positive for Covid19 has been tested.
"Kevin, at the moment he got Covid, it filled his condition and it was a mishap," Guardiola said on Monday.
"But that is normal because people who have gone through Covid in a short time feel so empty.
" It becomes gradually. He played his first 30 minutes and will start tomorrow. We will see how long it will take. He can play. "
Despite his family, De Bruyne should be fighting for a starting position at a club where competition for starting positions is extreme, with Guardiola's Bernardo Silva portrayed as the best player in the Premier League at the moment.
" He has to come back and fight for a position like everyone else, "said Guardiola.
" Kevin doesn't have to show himself without question, nothing for me, but he has to behave naturally again and show that he is back and do what "he does. It has to be every three days as it has for the last five or six years.
"Obviously the opponent is so important and he knows it, but Bernardo knows it and (Ilkay) Gündogan knows it and all the wingers and strikers know it .
"They realize that they have to play well (no matter if) play five minutes, 10 minutes or an hour and a half."
City have actually achieved the best position in Group An and Guardiola will likely make several changes for the game in Germany make as teenagers Cole Palmer, James McAtee, Romeo Lavia, Joshua Wilson, Esbrand and Conrad EganRiley will travel "minutes of play since we have five substitutes."
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