"Everybody is worried because I think it's something to do with his knee ligaments," Chelsea manager Jose Mourinho was quoted as saying by Sky Sports after Saturday's exhibition game.
Cole was injured five minutes after coming on as a second-half substitute. The star midfielder will undergo tests when the squad returns to London, but Mourinho's predictions are bleak.
"It's a problem because he is a big player for us. You could see his quality as a player," said Mourinho. "He is a player that I need but don't have."
"That's a real problem. If you tell me there is no problem with Joe Cole and we lose 10-0 then that is better," the Portuguese manager added.
"The problem today is that we don't want injuries, especially in pre-season."
The game was held in Chicago and marked the end of the Premiership champions' tour through the USA.
Mourinho took the opportunity to showcase his new signings, Michael Ballack and Andriy Shevchenko as starters, both of whom were substituted during the game.
While Mourinho was critical of the team's performance, he was more concerned with Cole's fitness.
"That's a real problem," he said. "If you tell me there is no problem with Joe Cole and we lose 10-0 then that is better.
Mourinho emphasized that the rigorous schedule had affected his team's stamina, but conceded to the MLS team's talent.
"They were faster, sharper than us and they were able to play a high tempo game against a team that tired and were slow," Mourinho said.
The only goal was scored by Dwayne De Rosario, for the Major League Soccer side in the 70th minute. Despite the side's performance Mourinho remained unfazed by the defeat.
"The result was not a surprise for me. I always want a better result and better performance but I am not surprised," he said.