Holden has been plagued by trouble with the same right knee in the past, missing almost two years of football after sustaining a major injury against Manchester United in 2011.
He went down hurt in the 18th minute of the Gold Cup final last night and was substituted by Klinsmann.
Klinsmann said: "We are very concerned about Stuart's situation.
"It looks like a very serious injury, but I'm not a doctor and I can't confirm it."
Former Germany striker Klinsmann added on ussoccer.com: "We'll get an MRI and he'll have all the tests done. Stu is a player that when something happens, he knows when something happens. Hopefully it's not as bad, but it's not looking good right now."
Holden wrote on Twitter after the match: "For all that know me + have supported me, I hope u know I will always prevail no matter what the outcome. Fingers crossed. Let's celebrate!"