Manchester City will once again be without first-choice centre-back pairing Eliaquim Mangala and Vincent Kompany when they face Borussia Monchengladbach in the Champions League.
Club captain Kompany and Mangala began City's opening five Premier League, with Pellegrini's side victorious on each occasion without conceding a goal.
Kompany suffered a calf strain as City spurned a lead to lose their Group D opener 2-1 to Juventus earlier this month and their subsequent form does not bode well.
Mangala went off at half-time with a muscular injury as West Ham left the Etihad Stadium with a 2-1 win, while Kompany withdrew from a planned return to the bench at Tottenham on Saturday.
He was forced to watch on as his team turned in a shambolic second-half performance and succumbed to a 4-1 loss.
But Argentina international duo Nicolas Otamendi and Martin Demichelis are set to continue in the heart of defence as Pellegrini cast doubt on Kompany's participation in Belgium's concluding Euro 2016 qualifiers next month.
"Vincent is an important player but just one player doesn’t make a difference," Pellegrini told a press conference, where he confirmed Gael Clichy, Fabian Delph, Samir Nasri and Wilfried Bony would also join his defensive duo on the sidelines.
"He is our captain and he started very well this season. I think it will be difficult for him to play for the national team next week."
There was some good news for Pellegrini on the injury front, as he confirmed David Silva and Joe Hart were fit to return from respective calf and back complaints.
Yaya Toure took part in training on Tuesday, showing no ill effects from the tight hamstring that curtailed his afternoon at White Hart Lane, while right-back Pablo Zabaleta is available for the first time this season following a knee ligament strain.
Pellegrini will be grateful to have such key figures available after the defeat to Juventus repeated a familiar theme of City flattering to deceive in Europe’s premier competition.
"We need to do our best if we are to recover the three points we dropped at home," the manager said.
"I don't think we have failed in Europe. We just lost a game against Juventus and now we have to try again."
Pellegrini himself might have failed to get to Germany on Tuesday, when he got off the team bus at Manchester Airport and immediately jumped in a taxi back to his Cheshire home .
"It was not important – just I have two passports and I brought the wrong passport," he explained to giggles.
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