Serena, who lost in the third round of singles Saturday, looked out of sorts from the moment the pre-match warm-up began. It was an odd scene, as the 32-year-old American had trouble collecting tennis balls from the ball kids and whiffed on some practice strokes.
The start of the match then was put off for about 10 minutes while Serena sat in her sideline chair and was examined by medical staff, including a check of her blood pressure. At one point, Serena hunched over and covered her face with her hands.
"I am heartbroken I'm not able to continue in the tournament," Serena said in a statement. "I thought I could rally this morning, because I really wanted to compete, but this bug just got the best of me."
During the delay, one of the Williamses' other sisters, along with Serena's agent and her hitting partner, left their seats in the stands.
Eventually, the second-round doubles match against Kristina Barrois and Stefanie Voegele began. With Serena serving in the third game, she was broken at love with four double faults. One of the best servers in the women's game, she hit serves that bounced before reaching the net.
At love-40 in that game, chair umpire Kader Nouni took the unusual step of climbing down from his perch and walking over to speak to Serena. She then served another double fault to trail 3-0.
Serena and Venus walked to the sideline holding hands, and Nouni announced to the crowd at No. 1 Court: "Ladies and gentlemen, unfortunately, Miss Williams has to retire."
Serena wiped away tears as she walked toward the court's exit.
"Unfortunately Serena has been feeling unwell for the past few days and she just couldn't play to her potential today," Venus said in a statement. "I'm really proud of her for trying because we just love playing doubles together. We are looking forward to coming back to Wimbledon next year."
Later, the Wimbledon referee's office and the WTA said that Serena had a viral illness.
Serena and Venus have won 13 Grand Slam titles together, including five at Wimbledon. In singles, the No. 1-ranked Serena owns 17 major titles, the most among active women.
The Associated Press contributed to this report.