Teams can name nine substitutes on bench in the League Cup semis and final after the EFL approved five substitutions per game. However, City had six players unavailable due to positive tests in their 3-1 Premier League win at Chelsea last weekend.
City's game at Everton last week was also postponed due to several positive cases in their camp, with the Manchester club joining Newcastle United, Sheffield United and Fulham among those who have suffered virus outbreaks in the top flight.
"We don't have many players," Guardiola told Sky Sports. "To play one, two games is okay, but if sustained for a long time - and you can use just 14 or 15 players - it will be more difficult.
"But... we have to adjust as much as possible. We don't have an alternative. The important thing is the guys who have COVID recover well and the others try to avoid it as much as possible."
The Premier League returned 40 new COVID-19 cases on Tuesday, the highest in a week this season, after two rounds of testing last week.
But despite the surging infections in England caused by a new variant of the virus, the Premier League has said games will be held as scheduled with the competition being allowed to continue during the national COVID-19 lockdown.
"It looks like we are an island inside the society. It's like everything is locked down except ourselves," Guardiola added.
"They [players] have to be careful what they do. Social distance, be careful and be lucky because even doing as best as possible, there are risks."
