Pablo Zabaleta will be out for a month after the Manchester City right-back suffered a knee injury in training.
Argentina international Zabaleta is set to miss the beginning of City's Champions League campaign and four Premier League games, starting with Sunday's trip to Everton.
It means Bacary Sagna, who has started the first two matches of the campaign, is set for his longest run in the City team since his arrival from Arsenal.
Zabaleta was on the bench for the 3-0 win over West Bromwich Albion and 3-0 success over Chelsea after he missed City's preseason tour because he was granted time off following the Copa America, and he will now have to wait several more weeks for his first appearance of the season.
Pellegrini told a news conference: "Pablo Zabaleta had yesterday a problem in his knee with his ligaments so he will be out for around one month."
However, Fabian Delph is in contention to make his competitive City debut against Everton.
The £8 million signing from Aston Villa suffered a hamstring injury 17 minutes into his first appearance in a City shirt, the 4-1 defeat to Real Madrid in Melbourne.
Now he has returned to training and Pellegrini added: "Fabian Delph returned this week on Wednesday to work with the whole squad so he doesn't have any problems."
While City's squad has been bolstered by the addition of the £31.5 million centre-back Nicolas Otamendi, who completed his move from Valencia on Thursday, Pellegrini said Vincent Kompany and Eliaquim Mangala will keep their places against Everton as he suggested he will pick an unchanged team.
City have started the season with back-to-back Premier League clean sheets and Pellegrini said he is happy with the way the defence has performed.
"In the way we are playing, it is impossible to move Kompany and Mangala and all the rest of the players from their positions," Pellegrini added. "They are in a good moment. We did not concede one goal in the last two games. We continue playing with the same."
City will equal a record of nine straight league wins, set in 1912, if they triumph at Goodison Park but Pellegrini said: "It matters to have three more points in the table. If that is a new record, that for me that is not important."