She's the third singles player on theU.S. Olympic women's tennis team with a knee injury.
Williams' sister Venus and Lindsay Davenport have already pulled out of next week's East West Bank Classic in Carson, California, with right knee injuries.
Serena Williams struggled from the start against the 85th-ranked Wozniak.
She first called for the trainer when trailing 5-2 in the first set.
She got the knee heavily taped and came out to finish the set, but appeared to struggle.
Wozniak held serve to win the set and won 11 straight points to take a 3-1 lead early in the second.
Williams appeared to injure the knee further while stretching for a backhand in the fifth game of the set and walked off the court.