When it was over, the world's No. 1-ranked player sounded almost relieved that she wouldn't have to try to win the Family Circle Cup for a third straight year.

"I'm really just dead," Serena Williams said Tuesday night after a shocking 6-4, 6-4 loss in her opening match against Jana Cepelova, a 20-year-old Slovakian ranked No. 78. "I need some weeks off where I don't think about tennis and kind of regroup. I've had a long couple of years, and I'm really a little fatigued."

Serena's spring break - "I'm going to go on a vacation for sure," she said - will come at a price.

The 32-year-old was trying to win her third straight Family Circle Cup title and fourth overall, putting her in the company of tennis legend Chris Evert, who won five straight FCC titles from 1974-78.

Serena won her 59th WTA singles title last week on hardcourts in Miami. But it wasn't the quick turnaround to green clay that did her in; she's made that transition before. She said it was the culmination of the last two years, when she's reclaimed her No. 1 ranking and won 18 titles after a nearly year-long layoff in 2011 due to illness and injury.

"There's just been so much in the last several years," said Serena, who lost for just the fourth time on clay to a player ranked outside of the top 75. "I just need to take a deep breath and regroup. I think actually it'll really help me for the rest of the clay-court season."

Former Family Circle Cup champions Venus Williams, Serena's older sister, and Samantha Stosur flirted with similar disaster. Each needed three sets and more than two hours to win. No. 8 seed Sorana Cirstea did lose, and hometown favorite Shelby Rogers put up a brave fight in a 7-5, 7-5 loss to No. 12 Daniela Hantuchova.

But the big story was Serena, who had received a first-round bye. She was quick to credit Cepelova, who played a $50,000 ITF event in Osprey, Fla., last week and did not even bring her coach with her to Charleston. But Serena might have lost to almost anybody on Tuesday; as it is, it was her worst loss since she fell to No. 111 Virginie Razzano in the French Open in 2011.

Williams, who had won her last 15 matches at the Family Circle Cup, sleep-walked through the first 20 minutes, dropping the first five games as a stunned crowd at Billie Jean King Stadium Court watched in silence.

Early in the second set, Serena called for a medical time out and a trainer examined her lower back and taped her left thigh. Williams rallied briefly, but Cepelova did not fold, mixing solid groundstrokes with timely drop shots.

"All credit to her," said Serena, who lost on Stadium Court for the first time since she had to retire against Yung-Jan Chan in 2007. "She did well today ... she played the best she can probably play."

Cepelova actually defeated 2010 Family Circle Cup champ Stosur, then ranked No. 16, in three sets in Doha earlier this year.

But even that didn't prepare her for the reality of upsetting the world's top player.

"No. No," Cepelova said when asked if she thought before the match that she could beat Serena. "Of course, if you go to the court, you have to have all head to win. But it was not on my . I was nervous and I was not thinking about my win today."

Serena's loss opens her side of the bracket for players such as No. 3-seed Sara Errani, No. 5 Sloane Stephens and No. 15 Madison Keys. Four former Family Circle champs - Stosur, Venus Williams, Sabine Lisicki and No. 2 seed Jelena Jankovic - lurk on the other side.

What has been Serena's Show on Daniel Island is now wide open. She'll be somewhere far away.

"I'm excited," she said. "I feel like I now have the time to just take a breath and the break that I really needed to take and go from there."

Tuesday's scores

Jana Cepelova d. No. 1 Serena Williams, 6-4, 6-4

Daniela Hantuchova d. Shelby Rogers, 7-5, 7-5

Shuai Zhang d. Su-Wei Hsieh, 3-6, 7-6, 7-6

Elena Vesnina d. Anna Schmiedlova, 6-1, 6-1

Vania King d. Julia Glushko, 4-6, 7-5, 6-3

Venus Williams d. Barbora Zahlavova Strycova, 6-3, 0-6. 7-5

Lourdes Dominquez d. Anabel Medina Garrigues, 6-3, 6-2

Andrea Petkovic d. Lesia Tsurenko, 6-7, 6-4, 6-1

Samantha Stosur d. Yaroslava Shvedova, 6-3, 5-7, 6-1

Marina Erakovic d. Nadia Petrova, 4-6, 6-3, 6-4

Shuai Peng d. Caroline Garcia, 6-2, 6-3

Teliana Pereira d. No. 8 Sorana Cirstea, 3-6, 6-3, 7-6

Eugenie Bouchard d. Alla Kudryavtseva, 6-2, 6-0

Lucie Safarova d. Virginie Razzano, 2-6, 6-4, 6-4

Wednesday's Stadium Court schedule

10 a.m.

Elina Svitolina vs. Sloane Stephens

followed by

Vania King vs. Sabine Lisicki

followed by

Sara Errani vs. Kiki Bertens

followed by

Chanelle Scheepers vs. Venus Williams

Not before 7 p.m.

Lauren Davis vs. Jelena Jankovic

followed by

Raquel Kops-Jones/Abigail Spears vs. Jarmila Gajdosova/Saisai Zheng