Donovan says that the Galaxy team is deep enough to cover Beckham even though he has provided a team-high five assists so far this season.
"When you have to travel the way we do - cross-country for a game like this - you can't expect someone his age to play three games in a week," he said.
"David has been hurt some of the time he's been here with us, too. It's obviously going to hurt us. His qualities aren't easily matched by other people. You can't just throw someone in and expect them to play the same way David plays.
"We've done a good job of filling voids when we needed to throughout the year, and we expect to do the same [on Wednesday]," Donovan added.
"Some people will be disappointed, some will be happy that he's not here. He obviously helps the team. [It's] part of sports, especially in our country. It's unfortunate for people who pay to see him, but it's part of sports."