Akanji was taken off at half time in the Citizens' 3-0 Premier League win over Nottingham Forest just over a week ago with a problem the defender has "struggled a lot" with over the last few months, according to Guardiola.
The 29-year-old has since missed Man City's last two games, including Wednesday's 2-0 Champions League defeat to Juventus, and Guardiola has confirmed that the Switzerland international is not ready to return this weekend.
Akanji's problem was initially unspecified by Guardiola, but the Catalan coach was asked specifically about what the defender is dealing with at Friday's press conference.
"Manu has discomfort in the area for the belly, the pelvis, the abductor. It doesn't feel good," said Guardiola.
Guardiola delivers Akanji, Ake injury updates
"But he made an incredible effort against Bournemouth. He and Nathan [Ake] weren't even half at their best, but helped us by playing there.
"Manu plays 45 minutes and steps back and says, 'I have to recover, or I can't compete'. He's a strong player and so reliable, but he cannot be there [on Sunday]."
Guardiola was also asked for an explanation as to why injury-prone defender Nathan Ake is facing another spell on the sidelines; the Dutchman pulled his hamstring in the closing stages of City's win over Forest.
"Why is Nathan injured again? Why? He played 90 minutes, and 90 minutes. Three days later after being on the massage table, one month and a half [out injured]. Training one day and a half, and recovery training sessions, 90 minutes, and 90 minutes," Guardiola explained.
The Catalan has suggested that if both John Stones and Akanji were fit and available, he would have been able to rotate Ake for specific games and would have subsequently given him more recovery time between matches.
"If I had John [Stones] and if I had [Akanji], Nathan would play 90 minutes, and then not play 90 minutes. When people say, 'Why did I make the substitutions against Feyenoord on 75 minutes?!' It was 3-0, and I have to take care of them, with their [injury] history like that."
Guardiola hints at defensive experiment for Manchester derby
Akanji and Ake are two of six Man City players ruled out of Sunday's Manchester derby along with Stones (foot), Rodri (ACL) and Oscar Bobb (leg fracture), while Rico Lewis is suspended after he was sent off in last weekend's 2-2 draw at Crystal Palace.
Guardiola now has just three recognised first-team defenders at his disposal - Kyle Walker, Ruben Dias and Josko Gvardiol - while 19-year-old academy graduate Jahmai Simpson-Pusey is also in contention to feature.
The Citizens boss - who admitted that he is questioning himself after City's midweek loss - has been left to mull over his options for the showdown with Man United, and has hinted that he may have to experiment slightly with his starting lineup by playing some players out of position.
"I don't know what I have to do - I need players," said Guardiola. "We have three [defenders] so let's see what happens today and tomorrow. We will have to have a think about it.
"Maybe a winger has to play as a full-back, or Matheus [Nunes] maybe can play as a full-back, or we play with five at the back where wing-backs are wingers. I don't know. We are thinking what to do, but the soul and spirit of the team is there."
"I am sad for the players," Guardiola added. "I know and completely understand our fans may be sad. This group of players have made an era and done things no one else has done. Broken records. I just call the supporters to be there until the end.
Guardiola 'accepts difficult situation' amid injury woes
"We have more injuries than ever and it's made me think that you need a squad of 45-50 players. It would be more expensive for the summer but maybe you need more depth of squad.
"The schedule is the problem, it's not the physios, doctors or players. This is the truth."
Asked if any of his players have recently been playing with injuries during the club's difficult run of form, Guardiola said: "No. I would say Kevin [De Bruyne] is coming back, last game was better than the previous one, step by step.
"Erling [Haaland] played all the minutes, which is unbelievable, and I don't know where we would be without him.
"All of them, it's so emotional from my point of view when I see them in the recovery and time spent in this period. It's remarkable and I'm there with them, I say 'you are good guys', they play well.
"It's a difficult situation but we have to accept it. I have to analyse a little bit more than just the results, the players are here, I want to stay close to them, not behind or in front, beside them. This is what I want to do."
Guardiola did not provide an update on either Mateo Kovacic or Phil Foden, but both players were named as unused substitutes for the midweek defeat to Juventus and are expected to be named in the matchday squad again on Sunday.
Man City sit fourth in the Premier League table - at the time of writing - and are eight points behind leaders Liverpool, who have a game in hand, while Man United are down in 13th spot with only 19 points - their lowest tally after 15 games since the 1986-87 campaign.
Written by
Oliver Thomas