Chelsea's pre-season program got off to a disappointing start when they lost 1-0 to the Major League Soccer All-Stars and midfielder Joe Cole suffered a knee injury.
The only goal at Toyota Park, just outside Chicago, came from Canadian international Dwayne De Rosario, who beat reserve goalkeeper Hilario with a shot from 18 metres in the 70th minute.
The game marked the end of the English champions' trip to the U.S., which included a week-long training camp in Los Angeles. Manager Jose Mourinho said the tough workouts had taken their toll on his players' legs.
"The team with the better conditioning won the game. They were faster, sharper and able to play at a high level going against a team that was tired, slow and it was difficult for our players to go 45 minutes. It was not a surprise," Mourinho told reporters.
England international Cole limped off with a knee injury five minutes after coming on as a second-half substitute. He left the stadium on crutches and will undergo tests when the squad returns to London.
"For me, Cole is the real problem of the day," Mourinho said. "I'm not a doctor, it's not my job. But everybody is worried."
New signings Michael Ballack and Andriy Shevchenko both started the game. Shevchenko, still recovering from a knee injury, looked rusty while Ballack began his new midfield partnership with Frank Lampard.
Ballack put striker Didier Drogba through on goal in the 28th minute, but the Ivorian's effort was ruled out for offside.
Youngsters Salomon Kalou and Jon Obi Mikel both appeared for the first time in a Chelsea shirt in the second half, two of Mourinho's six substitutions at the break.
Only Lampard, John Terry, Michael Essien and Geremi played the full game.
The match came to life after De Rosario's goal. Chelsea pushed forward for a late equaliser but Arjen Robben's header went just wide in the 90th minute and Ricardo Carvalho's stoppage-time attempt was saved at point-blank range by goalkeeper Joe Cannon.
Chelsea visit Dutch club Feyenoord on Tuesday, host Celtic on Wednesday and face Liverpool in the Community Shield on Sunday.