The 13-time major winner was rushed to Cedars-Sinai Medical Center in Los Angeles for the removal of a hematoma, or internal hemorrhage. That followed the discovery and treatment last week of a blood clot in her lungs.
Williams has not played a WTA match since injuring her right foot just days after winning Wimbledon title in July.
The clot, known as a pulmonary embolism, surfaced during her return to Los Angeles following doctor appointments in New York for ongoing issues with her foot.
BRENNAN: Future remains unclear for Serena
People magazine first reported on Williams' condition, quoting spokeswoman Nicole Chabot as saying Williams underwent "emergency treatment" Monday for a hematoma suffered as a result of treatment for "a more critical situation," the pulmonary embolism.
Williams, who said last month she hoped to return by spring, has now pushed that back to "early summer."
"This has been extremely hard, scary, and disappointing," she said in a prepared statement. "I know I will be OK, but am praying and hoping this will all be behind me soon. While I can't make any promises now on my return, I hope to be back by early summer. That said, my main goal is to make sure I get there safely."
The statement called the hematoma an "unexpected scare" and said Williams is "recuperating at home under strict medical supervision."
Since snagging snagged a fourth Wimbledon crown, women's tennis' biggest star has been increasingly star-crossed.
The star cut her foot on glass at a restaurant in Germany that has required two surgical procedures. Just last week, Serena, who has dropped from No. 1 to No. 11 in the rankings, was cleared to remove the temporary boot from her foot and had started light rehabilitation. Then came Wednesday's news.
"Thankfully everything was caught in time," her agents said in a statement.
The tennis star attended Sunday night's Elton John AIDS Foundation Academy Awards Viewing Party. On Tuesday night, Williams posted on her Twitter account, "Tough day." A few minutes later, she retweeted Kim Kardashian.
Mark Adelman, chief of vascular surgery at NYU Langone Medical Center, said a patient with a pulmonary embolism would need to take an anticoagulant for six to 12 months but could play sports on the medication.
"A blood clot can occur in any vein or extremity, most commonly in the leg, and can travel to the lung," Adelman wrote in an e-mail. "Prior surgery, air travel, prolonged sitting, birth control pills, obesity and pregnancy can predispose a patient to a blood clot in the leg that can travel to the lung."
Several top players, among them world Nos. 1 and 2 Caroline Wozniacki and Kim Clijsters, expressed concern for Williams via Twitter.
"My thoughts are going out to her, hope she is ok!" Wozniacki wrote.
"Just read about Serena!!!! Very scary, hope she is ok!fingers crossed!" Clijsters said.
The WTA also issued a statement: "We are very heartened to hear … Serena is now recovering and on the road to full health and a possible return to professional tennis in early summer. Serena is a champion on and off the court, and we along with her millions of fans wish her a speedy recovery."
Despite injuries and setbacks, Williams has demonstrated a knack for reasserting her place atop the sport after lengthy layoffs or less than ideal form, as she did when she won the 2007 Australian Open unseeded and ranked 81st.
The latest impediment also could jeopardize her participation at the 2012 Olympics. She and her sister, Venus Williams, must play in Fed Cup this year and next or risk losing eligibility for the U.S. Olympic team in London.
"She's had a rough eight months," said Jim Curley, the U.S. Open tournament director, who was in Chile for the USA vs. Chile Davis Cup tie this weekend. "You can only focus on her getting better. Tennis is completely secondary at this time."
Williams has a wide range of business, fashion and charitable interests that keep her in the public eye even when she's not on the court. Since winning her first Grand Slam title in 1999, she has struggled with injuries on several occasions only to come back to win more championships.
"Serena is a champion and a fighter," tennis great Billie Jean King said in a statement. "I know she is the kind of person who faces challenges with complete optimism and guts and I don't think this situation will be any different for her."