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.
"I am really just dead," said the 32-year-old American. "I need some weeks off where I don't think about tennis and can kind of regroup. I've had a long couple of years."
Williams, who won this event in 2013, 2012 and 2008, also had her 15-match tour win streak snapped.
"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.
She advances to face Elena Vesnina of Russia, who beat another Slovakian, Anna Schmiedlova, 6-2, 6-1.
Williams, 32, blasted four aces but committed three double faults. She won just 12 of 28 points on her second serve.
You’ve reached your limit of {{free_limit}} free articles this month.
Subscribe now for unlimited access.
Already subscribed? Log in
Subscribe to read the full story →
Smart Quarterly
₹900
3 Months
₹300/Month
Smart Essential
₹2,700
1 Year
₹225/Month
Super Saver
₹3,900
2 Years
₹162/Month
Renews automatically, cancel anytime
Here’s what’s included in our digital subscription plans
Exclusive premium stories online
Over 30 premium stories daily, handpicked by our editors


Complimentary Access to The New York Times
News, Games, Cooking, Audio, Wirecutter & The Athletic
Business Standard Epaper
Digital replica of our daily newspaper — with options to read, save, and share


Curated Newsletters
Insights on markets, finance, politics, tech, and more delivered to your inbox
Market Analysis & Investment Insights
In-depth market analysis & insights with access to The Smart Investor


Archives
Repository of articles and publications dating back to 1997
Ad-free Reading
Uninterrupted reading experience with no advertisements


Seamless Access Across All Devices
Access Business Standard across devices — mobile, tablet, or PC, via web or app
