Serena, the 32-year-old world number one singles player, called the doctor to Court One just after she and Venus had warmed up for their second round match against Kristina Barrois and Stefanie Voegele.
But after serving up four double faults, a clearly distressed Serena, who was unsteady on her feet, was led by the hand by Venus off court where the sisters then conceded the tie at 3-0 down.
"We were all looking forward to a great match. From the bottom of my heart, I thank all of the fans for their cheers and understanding. I look forward to returning to Wimbledon next year."
Venus expressed sympathy for her younger sister.
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"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.
Serena was in tears courtside as she consulted with the doctor and physio before the tournament referee and supervisor were also called out in a reflection of her status in the sport.
After a 15-minute delay, during which she also had her blood pressure monitored, the match got underway but it was clear it would be a brief affair.
Umpire Kader Nouni, having already come down from his chair to talk to the Americans, announced that Serena was retiring from the match through illness with the sisters trailing 3-0.
The American has suffered health problems in the past, notably enduring life-threatening blood clots in 2011.