The unseeded Williams was scheduled to meet 22nd-seeded German Sabine Lisicki in a second-round match on Day 3, but Lisicki, instead, received a walkover into the round of 32.
Williams said she has been diagnosed with Sjogren's Syndrome, which is a disease that creates fatigue and joint pain.
The 31-year-old Williams has battled injuries for most of this 2011 season and hadn't played any tennis since losing in the fourth round at Wimbledon last month before returning with an easy opening-round victory against Russian Vesna Dolonts here on Monday night. "I enjoyed playing my first match here and wish I could continue, but right now I am unable to," Williams said in a statement. The former world No. 1 and seven-time Grand Slam champion titled here back-to- back in 2000 and 2001 and is also a two-time runner-up in Flushing. "I was really looking forward to the match," Lisicki said. "I love those big matches and playing against Venus. On the court Wednesday, last year's U.S. Open runner-up Vera Zvonareva posted a second-round win.
A big Day-3 upset came when American teenager Christina McHale upended eighth- seeded Frenchwoman Marion Bartoli 7-6 (7-2), 6-2. Ninth-seeded former French Open runner-up Samantha Stosur avoided an upset by topping American teen Coco Vandeweghe 6-3, 6-4, while 13th-seeded Chinese Peng Shuai cruised past Bulgarian Tsvetana Pironkova 6-2, 6-4, and 19th-seeded German Julia Goerges grounded Spaniard Laura Pous-Tio 6-3, 6-1.
Meanwhile, 24th-seeded Russian Nadia Petrova handled Slovenian Polona Hercog 6-2, 6-4; 25th-seeded Maria Kirilenko leveled fellow Russian Vera Dushevina 6-1, 6-2; 27th-seeded Czech Lucie Safarova overcame 16-year-old Illinois native Madison Keys 3-6, 7-5, 6-4; and a 30th-seeded Medina Garrigues grounded Britain's Laura Robson 6-2, 6-3 at the year's final Grand Slam event.
Two-time champion Venus Williams withdrew from the U.S. Open prior to her second-round match because of an autoimmune disease, while 19-year-old American Christina McHale upset No. 8 seed Marion Bartoli in straight sets.
Williams, who came into the tournament unseeded for the first time since 1997, was set to play No. 22 seed Sabine Lisicki of Germany this afternoon.
McHale, from Englewood Cliffs, New Jersey, beat Bartoli of France 7-6 (7-2), 6-2 on the grandstand court at the National Tennis Center in New York. She'll play 25th-seeded Maria Kirilenko of Russia in the third round.
McHale Ranked 55th
McHale is ranked 55th by the WTA Tour and beat No. 1-ranked Caroline Wozniacki of Denmark this month. Bartoli reached the semifinals of the French Open and the quarterfinals of Wimbledon this year.
The Bryans won the Wimbledon and the Australian Open doubles titles this year. Vera Zvonareva, the No. 2 seed from Russia who was runner- up at last year's U.S. Open, beat Ukrainian Kateryna Bondarenko 7-5, 3-6, 6-3 in Arthur Ashe Stadium to advance to a third-round match with 30th-seeded Anabel Medina Garrigues of Spain.
Soderling Out
Soderling was replaced by Rogerio Dutra Da Silva of Brazil, who won when Sorenson quit the match with cramps trailing 6-0, 3-6, 6-4, 1-0.
Roddick at Night
Andy Roddick plays his first-round match under the Ashe Stadium lights tonight against fellow American John Russell. Williams has played in only four tournaments since Wimbledon last year and has dropped to No 36 in the world rankings. Robin Soderling was another high-profile withdrawal from the tournament, pulling out with illness shortly before he was due to play his first-round match yesterday against the Irishman Louk Sorensen.