Twelve of City’s squad have played international football over the past fortnight and Guardiola concedes some of them are tired.
The fitness issues do concern him but the Spaniard, whose side face Crystal Palace in the Premier League today and play Borussia Monchengladbach next week, knows he has to find ways to cope.
He said: “As quickly as possible (we need them) involved again in our reality, but they need time. They are human beings.
“Today the schedule is so stressful for the players. I rest but the players don’t. It is so demanding - 11 months and after that two or three weeks off and then 11 months again, and you cannot lose or play badly.
“That is why you have to handle that sometimes. When you see they are down, take them up, but every player is different.
“When some of them come back from the national team their regeneration is quicker than others, for the physical condition, for many many things.
“We have a game and a final in Germany in three or four days and three days later we have Burnley, so everyone is going to play.”
Guardiola has no fresh injury concerns but admits his South American contingent - Sergio Aguero, Fernandinho, Nicolas Otamendi and Pablo Zabaleta - are feeling the strain most.
He said: “All the players came back good, fit but the players who played 90 minutes and (another) 90 minutes are tired, especially the South American players.”
City slipped up on their last outing, conceding a late equaliser to Middlesbrough to lose top spot. They have won just one of their last five games in the league and Guardiola expects another difficult game against Alan Pardew’s Palace at Selhurst Park.
He said: “(It is a) really tough game, (and a) coach with a lot of experience in England. They play a lot with (Christian) Benteke, second balls with all the wingers, with (Andros) Townsend, (Wilfried) Zaha.
“The toughest games we will play now (are) away but we know the situation. We want to be there and stay there with the big teams in the Premier League. We have to win.”
Captain Vincent Kompany could be in contention after being fit to report for Belgium but not participating in their matches against Holland and Estonia as a precaution.
Palace are 16th in the table having won just three times in 11 games but Guardiola claims that is irrelevant.
He said: “When I see a team I never look at the position of the table. I see the games, I try to analyse what they do and especially when they play good, they are strong, it is not easy.”
Palace lost all three games against the Manchester side last year - twice in the league and once in the Capital One Cup - but Pardew believes they can come out on top on Saturday.
“We have watched most of City’s games. They have the ability to win the league and hopefully we will put a dent in it.”
Pardew does not believe his team are in a relegation battle, although he is keen for a change of fortune.
He said: “We need to improve (all over), there is no doubt about that. I think the result at Burnley (a 3-2 defeat) was a big blow for us because it was a game where we played well, got ourselves back into and we got carried away thinking we should try and win the game with seconds remaining.
“I don’t think that is a bad thing but we left ourselves short and that has put pressure on us, pressure we are going to have to deal with.
“We are in a position in the league which is false and we need to rectify that before we get to February.
“There are some fantastic players in our team. I am not even thinking that we are in a relegation battle, to be honest. We have just got to make sure that in the next few weeks we get some important results.
“Two wins could take you to mid-table, there is a long way to go yet.”