Michael Cheika on Thursday announced nine changes to his Argentina side to take on Australia in their Rugby Championship opener in Mendoza but was unable to recall one key player.
Veteran fly-half Nicolas Sanchez suffered an injury relapse after returning to training this week.
"It's very sad. It's the same situation that happened during the international window with Scotland," Australian-born Cheika said.
Sanchez had begun the first Test against Scotland -- a 26-18 victory -- but was forced off midway through the first half with a calf tear and has not played for the Pumas since.
"Nico is a very important player for this team and as his coach I have to take responsibility for a repeat injury," said Cheika, adding that Sanchez needed more treatment and time to recover.
Santiago Carreras remains at outside half for the game on Saturday.
Tomas Cubelli, who injured a thigh in the warm-ups to the first Scotland Test and missed the series, does return at scrum-half.
There is an entirely new front row from the team that started against Scotland last month in the decisive third Test, won 34-31 by the Pumas thanks to a last-gasp Emiliano Boffelli try.
Captain Julian Montoya and props Francisco Gomez Kodela and Nahuel Tetaz Chaparro come in for Agustin Creevy, Tomas Gallo and Joel Scalvi.
Marcos Kremer replaces Facundo Isa in the back row with Juan Martin Gonzalez picked ahead of Santiago Grondona at lock.
Boffelli remains on the left wing but Santiago Cordero replaces Bautista Delguy on the right flank. Jeronimo De La Fuente comes in at inside center instead of Matias Moroni.
"There's a lot of competition going on inside the team and it's up to us to try to select the best team," said Cheika.
Argentina host the Wallabies in Mendoza on Saturday before both sides move to San Juan for another Pumas home match the following weekend.
ARGENTINA (15-1): Juan Cruz Mallia; Santiago Cordero, Matias Orlando, Jeronimo De La Fuente, Emiliano Boffelli; Santiago Carreras, Tomas Cubelli; Pablo Matera, Marcos Kremer, Juan Martin Gonzalez; Tomas Lavanini, Matias Alemanno; Francisco Gomez Kodela, Julian Montoya (capt), Nahuel Tetaz Chaparro
Replacements: Agustin Creevy, Thomas Gallo, Joel Sclavi, Santiago Grondona, Rodrigo Bruni, Lautaro Bazan Velez, Tomas Albornoz, Matias Moroni