Isner, the top-ranked American in the world at No. 13, suffered the injury during a 6-4, 6-4 loss to Ryan Harrison at the Sydney International.
He said after that setback he was considering pulling out of the Australian Open.
"I have been feeling some discomfort in my knee and have recently learned that I have a bone bruise," Isner said in a statement released by Australian Open officials Thursday. "Doctors have told me that continuing to play on the knee could result in a more serious injury."
2014: The Year in Music [PHOTOS]