(CNN) -- It was deja vu for the Williams sisters at the French Open -- but not in a good way. 

A mouthwatering third-round clash between seven-time grand slam champion Venus and 17-time major winner Serena was ruled out when the former lost to unseeded Slovakian Anna Schmiedlova 2-6 6-3 6-4 in early play in Paris on Wednesday. 

Then hours later, Serena -- also the defending champion and world No. 1 -- fell to Spain's Garbine Muguruza 6-2 6-2, her worst ever grand slam performance. 

In 2008, the siblings were also defeated on the same day at Roland Garros, their least productive major. The last time it happened was at Wimbledon in 2011. 

An 18th grand slam singles crown for Serena would have tied her with legends Chris Evert and Martina Navratilova but the younger of the tennis playing sisters has now been upset in consecutive majors. 

Venus has been hindered by debilitating autoimmune disease Sjogren's Syndrome in recent years though she looked solid in her first round match against the promising Swiss, Belinda Bencic. 

The siblings join other big names who've already been upset at the tournament, including Australian Open champions Stan Wawrinka and Li Na, as well as Kei Nishikori and Caroline Wozniacki. 

Defeat for Serena meant it was the first time in the Open era that the top two women's seeds had fallen before the third round. 

"I don't think anything worked for me today," a dejected Serena told reporters at her post-match press conference. 

"It was one of those days. You can't be on every day, and, gosh, I hate to be off during a grand slam but it happens. It's not the end of the world. 
Who was won seven times?
 seven-time grand slam champion Venus