Matches are coming thick and fast after a shortened off-season after the coronavirus-hit 2019-2020 campaign, with City due to host Leicester City in the Premier League on Monday (AEST) on the back of Friday's (AEST) Carabao Cup victory against Bournemouth.
City will be without Gabriel Jesus as its injury list grows – Sergio Aguero, Bernardo Silva, Joao Cancelo and Oleksandr Zinchenko are all recovering from fitness issues.
Guardiola, whose City was afforded an extra week of recovery before opening its season with victory at Wolverhampton Wanderers after a run to the UEFA Champions League quarter-finals, hit out at the football calendar, saying: "Nobody cares about the players. It is about the business. The reality is what it is.
"It is not just Man City, it is all the clubs and countries. Nobody cares about the players.
"Everyone – the Premier League, UEFA, EFL – has defended their own business and position.
"The players had a two-week pre-season and now they have to play every three days for 11 months. We will not change anything saying the opposite.
"I understand it is an exceptional situation for everyone – restaurants, theatres, cinemas, museums.
"Everyone is struggling. We are not an exception. We have to believe in what we are doing and try and play a good game.
"We have three players who came back from national teams injured. We cannot control that. They let them play two games in four days without preparation. They are not machines."
While frustrated with the demands on players, Guardiola heaped praise on City star Riyad Mahrez ahead of his reunion with former club Leicester.
Mahrez, who won the 2016 Premier League title with Leicester, made his first appearance of the season in the 2-1 win over Bournemouth on Friday (AEST) after a positive coronavirus test during pre-season.
"Riyad is an exceptional player. He arrived late after the positive COVID-19 test only training for a few days before Wolves but I know how important he is for us," Guardiola said.
"For the quality, the passes and especially his mentality and he is aggressive to score goals. We will train the guys who didn't play [against Bournemouth] and we will see the way we are going to play and then which players will play."