But she broke the 44th-ranked Zakopalova 12 times, including the final game.
Sharapova is trying to complete a career Grand Slam at age 25. She never has made it past the semifinals at Roland Garros.
Zakopalova never before went beyond a major's second round.
Li Na's French Open title defense ended Monday with a 3-6, 6-2, 6-0 fourth-round loss to 142nd-ranked qualifier Yaroslava Shvedova of Kazakhstan on a blustery day at Roland Garros.
Shvedova, a doubles specialist who teamed with Vania King to win Wimbledon and the U.S. Open in 2010, became only the ninth qualifier to make it to the quarterfinals at Roland Garros. This matches the furthest she's ever gone in a Grand Slam singles draw.
The seventh-seeded Li's loss leaves no former French Open champions left in the women's draw. Last year at Roland Garros, she became the first player from China to win a Grand Slam singles title.
Jo-Wilfried Tsonga followed up a long night of worrying with a short day of tennis.
In the end, everything turned out OK for France's favorite player.
The No. 5 seed returned to Roland Garros on Monday and finished off a five-set victory over No. 18 Stanislas Wawrinka, quickly dropping a service break but rebounding to win the last two games of a match that was suspended by darkness the night before.
"To a certain extent, it was a bit of a nightmare until the moment I hit my first ball, because before that, I had a thousand questions in my head," Tsonga said. "I really wanted to win that match, and it was very difficult."
Tsonga led 4-2 in the fifth when play resumed and won 6-4, 7-6 (6), 3-6, 3-6, 6-4 to advance to the French Open quarterfinals, with a meeting against No. 1 Novak Djokovic up next.
Tsonga's five sets against Wawrinka lasted 4 hours, 6 minutes, most of it played in the dimming light the night before. Still, the Frenchman said he felt as if the hardest work came after the restart.
"I've spent more energy in four games today than in five sets yesterday," he said.