The former world number one made a winning comeback from an eight-month injury layoff at the Nasdaq-100 Open earlier this month, but pulled out of the Charleston claycourt event on Thursday despite an easy second round victory.
"The official diagnosis by the doctor was that he was shocked that I was playing this many tournaments in the beginning," Williams said.
"He was wondering why I had decided to do so many back to back to back to back."
Williams made her return to tennis after knee surgery on March 26 in Miami and successfully defended her title at the NASDAQ-100 Open.
She then travelled up the coast for the Amelia Island championship, making the transition to the claycourt season, where she fell to Nadia Petrova in the quarter-finals.
Williams was runner-up
"I'm really disappointed because I really like the fans here, and every year I just love coming back here," she said in a statement released by women's tennis organisers the WTA.
"I just love playing here and I've done well, so I'm very, very disappointed."
However, Williams said she was confident the injury would not prove to be an ongoing problem.
"(The doctor) said it's not my knee that's the problem. It's just that obviously I've been playing well and playing a lot of matches, and (my left knee) got a little fatigued," she said.
Williams' next scheduled WTA Tour event is the Telecom Italia Masters in Rome the week of May 10.
