Arturo Vidal and Alexis Sanchez are doubtful for Chile's opening World Cup qualifying game against Brazil in Santiago on Thursday.
Both players were pivotal for La Roja in the Copa America triumph this summer but are struggling with injuries.
"Neither Vidal nor Alexis are confirmed for the Brazil game," Chile coach Jorge Sampaoli told newspaper La Tercera. "Neither player has been in full training since joining the squad this week."
Sanchez scored twice for Arsenal in Sunday's 3-0 Premier League win over Manchester United but left the field late in the second half with a groin problem.
Vidal came on as a second-half substitute in Bayern Munich's 5-1 victory over Borussia Dortmund on Sunday but had missed his team's previous game - a 5-0 Champions League triumph over Dinamo Zagreb - with a knee injury.
Sampaoli is not optimistic over either player.
"Right now I see Arturo's participation highly doubtful, especially for the first game," he said. "The next few hours will be vital to determine if he can play.
"Alexis has the same risk as Arturo."
Sampaoli could rest the two players in view of Tuesday's game against Peru in Lima knowing that with or without them, his team face a big task against Brazil.
Chile were eliminated by Thursday's rivals at the 2014 World Cup on penalties and the two sides did not face each other at the Copa America with Brazil losing in the quarter-final stages to Paraguay.
"The World Cup is in the past," Sampaoli said. "The Copa America is in the past. We start from zero and there's no point in looking back.
"We expect difficult qualifiers and we need to be ready."
Sampaoli anticipates an especially hard game on Thursday.
"Any team in the world that plays against Brazil finds it difficult to overcome them," Sampaoli said. "They will certainly qualify for the World Cup.
"We need to make life difficult for a side that have very good players. The game will depend on whether we can limit Brazil.
"Brazil are a national team that throughout history have proved to be one of the best in the world. However, the only result I think about is a win.
"We have prepared ourselves to win this game."
Brazil travel to Santiago's Estadio Nacional having won 49 of their 70 meetings against Chile. They also won last month's friendlies against the United States and Costa Rica.
"This is the most difficult qualifier," Brazil right-back Dani Alves said on www.cbf.com.br. "World Cup qualifiers are challenging.
"We have a young team but I'm confident that we can do well."
Brazil must overcome the absence of Barcelona striker Neymar, who is suspended for the opening two qualifiers.
To complicate matters for Brazil coach Dunga, Liverpool star Philippe Coutinho is out injured, with Kaka taking his place in the squad.
Zenit St. Petersburg's Hulk, who scored the winner against Costa Rica last month, is expected to lead Brazil's attack.