Youkilis returned to Boston's Fort Myers, Fla. training camp to undergo an MRI, and hopes are the ankle is just sprained.
"He's a huge part of this ball club," Johnson said. "But also we don't want to take any chances. Ankles can linger, and that's something that needs to be addressed right away. He played with kind of a sprained ankle the other night."
Johnson added that Youkilis did not injure the ankle during the wild celebration after Tuesday's comeback 6-5 victory over Puerto Rico.
Youkilis is the fourth U.S. player out of the event with an injury.
The others are Boston second baseman Dustin Pedroia (abdominal injury), Atlanta third baseman Chipper Jones (abdominal injury), and Florida Marlins reliever Matt Lindstrom (right rotator cuff strain).