Serena Williams continues her quest for a record-equalling 24th Grand Slam title in the French Open third round on Friday, while Stefanos Tsitsipas faces the first real test of his title credentials against John Isner.

Russian second seed Daniil Medvedev and Alexander Zverev are also in action, while Victoria Azarenka will be looking to extend her best Roland Garros run since 2015.

The 39-year-old Williams saw yet another of her potential title rivals exit the tournament on Thursday, as world number one Ashleigh Barty hobbled out during the second round with a hip injury.

After Naomi Osaka's shock withdrawal, Simona Halep failing to start the tournament through injury and early losses for Bianca Andreescu and Angelique Kerber, none of the players who have beaten Williams in Grand Slam finals since her last title in the 2017 Australian Open are still in the competition.

The former world number one, still just one short of Margaret Court's all-time record of major trophies, faces fellow American Danielle Collins for a place in the last 16.

Williams beat Mihaela Buzarnescu in three sets in the second round
Williams beat Mihaela Buzarnescu in three sets in the second round AFP / MARTIN BUREAU

Williams won her only previous meeting with Collins, a Roland Garros quarter-finalist last year and 2019 Australian Open semi-finalist, in Melbourne earlier this year.

She says the pair get on well off the court, but it's unlikely the three-time French Open winner will take it easy on her friend on Court Philippe Chatrier.

"She (Collins) has been playing well," said Williams. "She's also a really awesome person off the court. I love seeing her in the locker room.

"Ideally it would be great if we didn't have to play each other, because I always want her to do super well, so... It's fine, though."

Williams could face Azarenka for a 24th time in the quarter-finals, with a chance of revenge for her US Open last-four defeat last year, but the Belarusian faces a tricky last-32 tie first up on Chatrier against Madison Keys.

Tsitsipas will have to return well against Isner on Friday
Tsitsipas will have to return well against Isner on Friday AFP / Christophe ARCHAMBAULT

Greek star Tsitsipas is well-fancied to reach his maiden Grand Slam final, with Rafael Nadal, Novak Djokovic and Roger Federer all in the other half of the draw, and with his task made easier by two-time runner-up Dominic Thiem's shock first-round defeat.

The fifth seed cruised through his opening two matches in straight sets against Jeremy Chardy and Pedro Martinez, but should face a far tougher test in Friday's night match against big-serving Isner.

The hot and bouncy conditions could play into the American 31st seed's hands.

"I'm sure he can serve well right now," admitted Tsitsipas, who has enjoyed a brilliant clay-court season, winning the Monte Carlo Masters, the ATP event in Lyon and reaching the Barcelona Open final, where he lost to Nadal despite holding a match point.

The 22-year-old made the semi-finals last October before losing a five-set epic to Djokovic.

Medvedev had never won a French Open match until this week, but has found his form this time around and faces the United States' Reilly Opelka on Court Suzanne Lenglen.

German sixth seed Zverev has not been at his best so far, but came back from two sets down in the first round against Oscar Otte before edging Russian qualifier Roman Safiullin in three tight sets.

He takes on Serbia's Laslo Djere.

Elsewhere on Friday, women's world number four Aryna Sabalenka, the highest-ranked player left in the draw, plays Anastasia Pavlyuchenkova.

Former men's world number four Kei Nishikori of Japan meets Swiss qualifier Henri Laaksonen after spending more than eight hours on court over the first two rounds.