Serena Williams is back against her second Romanian opponent in a row, while Coco Gauff and Venus Williams team up in the doubles.
The men's draw sees Daniil Medvedev and Stefanos Tsitsipas playing.
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Serena Williams was in mediocre form as she started her match against Irina Begu, but by the time she was into the second set she easily dominating her 30-year-old opponent. Williams needs just one more title to reach the magic 24, but will need to keep her standards high against Mihaela Buzarnescu.
Elsewhere, Venus Williams and Coco Gauff are going to double up against 13th seeds Ellen Perez and Zheng Saisai in the doubles.
Greek fifth seed Stefanos Tsitsipas will take on Spaniard Pedro Martinez in search of a place in the fifth round.
Karen Kachanov has threatened to become a stalwart in the top 10 in previous years but comes to Roland Garros as the number 23 seed. He has talent, but consistency is what he needs if he is to build on his four ATP titles, including one won here in Paris.
But he faces a difficult opponent, when he faces Kei Nishikori, at 31, six years his senior, who only six years ago was ranked as the number four player in the men's game.
To get your Brit fix on Wednesday you'll have to turn to the doubles.
On Court 2 is Cameron Norrie and Jonny O'Mara, who will face the home pair of Nicolas Mahut and Pierre-Hugues Herbert.
Heather Watson has been knocked out of the singles, but is paired with Anna Blinkova against ninth seeds Giuliana Olmos and Sharon Fichman.
Czech women's player Marketa Vondrousova takes on Harmony Tan in the first match on Court Philippe-Catrier on Wednesday morning.
In 2019 she was the first teenage WTA Grand Slam finalist since Caroline Wozniacki, and also has a WTA singles title to her name.
With the coronavirus on the wane in Europe and North America, this could be her chance to start moving up the rankings from her current 21st ranking.
Order of Play - from 10am UK time
- Harmony Tan v Marketa Vondrousova
- Karen Kachanov v Kei Nishikori
- Serena Williams v Mihaela Buzarnescu
- Tommy Paul v Daniil Medvedev
- Alexander Zverev v Roman Safiullin
- Polona Hercog v Caroline Garcia
- Stefanos Tsitsipas v Pedro Martinez
- Aliaksandra Sasnovich v Aryna Sabalenka
- Daria Kasatkina v Belinda Bencic
- Henri Laaksonen v Roberto Bautista Agut
- Victoria Azarenka v Clara Tauson
- Enzo Couacaud v Pablo Carreno Busta
- Katerina Siniakova v Veronika Kudermetova
- Fabio Fognini v Marton Fucsovics
- Mackenzie McDonald v Cristian Garin
- Elena Rybakina v Nao Hibino
- Tamara Zidansek v Madison Brengle
- Casper Ruud v Kamil Majchrzak
- Filip Krajinovic v John Isner
- Anastasia Pavlyuchenkova v Ajla Tomljanovic
- Laslo Djere v Miomir Kecmanovic
- Paula Badosa v Danka Kovinic
- Leylah Fernandez v Madison Keys
- Petra Martic and Shelby Rogers v Timea Babos and Vera Zvonareva
- Alicja Rosolska and CoCo Vandewegh v Andreea Mitu and Yulia Putintseva
- Alejandro Davidovich Fokina v Botic Van de Zandschulp
- Aleksandra Krunic and Martina Trevisan v Karolina Pliskova and Kristyna Piskova
- Alexei Popyrin and Jordan Thompson vs Tomislav Brkic and Nikola Cacic
- Sorana Cirstea v Martina Trevisan
- Pierre-Hugues Herbert and Nicolas Mahut and Cameron Norrie and Johnny O'Mara
- R Opelka v J Munar
- Thiago Monteiro v Steve Johnson
- Federico Delbonis v Pablo Andujar
- Danielle Collins v Anhelina Kalinina
- Marcos Giro v Guido Pella
- Salma Djoubri and Oceane Dodin v Amanda Anisimova and Anastasia Potapova
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Watch all the action from the 2021 French Open live on Eurosport, eurosport.co.uk and the Eurosport app with 13-time champion Rafael Nadal eyeing a remarkable 14th title at his favourite event and 2020 Roland Garros sensation Iga Swiatek aiming to replicate her stunning triumph in Paris.
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