The 20-year-old Slovakian Cepelova shocked defending champion Williams 6-4, 6-4 in a second-round match at the clay court tournament in Charleston.
The 17-time Grand Slam winner Williams complained about being mentally fatigued after the 84 minute contest.
Williams, who won this event in 2013, 2012 and 2008, also had her 15-match tour win streak snapped. source
Williams was fresh off winning her sixth Miami title and 59th singles crown after beating world No. 2 Li Na, of China, on the weekend.
“I actually made the turnaround really good,” Williams said. “Obviously things didn’t go great out there.”
Unseeded Cepelova, who appears to be headed for a breakout year, was facing Williams for the first time. Cepelova won 55 percent of her first serves and 71 of 136 total points.