The second 2021 Charleston Open (branded as the MUSC Health Women's Open for commercial reasons) was a tournament on the 2021 WTA Tour. It was played on outdoor green clay courts in Daniel Island. It was held one day after the 48th edition ended and was a replacement tournament for other tournaments that were not held because of travel restrictions, and organised by Charleston Tennis with a single-year licence in 2021, held at Family Circle Tennis Center from April 12 to 18, 2021.[1]
See main article: 2021 MUSC Health Women's Open – Singles.
Astra Sharma def. 
Ons Jabeur, 2–6, 7–5, 6–1See main article: 2021 MUSC Health Women's Open – Doubles.
Hailey Baptiste / Caty McNally def. Ellen Perez / Storm Sanders, 6–7(4–7), 6–4, [10–6]| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
| Tunisia | Ons Jabeur | 28 | 1 | |
 Poland | Magda Linette | 51 | 2 | |
| Shelby Rogers | 52 | 3 | ||
 France | Alizé Cornet | 59 | 4 | |
 Japan | Misaki Doi | 77 | 5 | |
| Australia | Ajla Tomljanović | 78 | 6 | |
| Lauren Davis | 79 | 7 | ||
| Madison Brengle | 81 | 8 |
The following players received wildcards into the main draw:
The following player received entry as a special exempt:
The following players received entry from the qualifying draw:
Amanda Anisimova → replaced by Caty McNally
Irina-Camelia Begu → replaced by 
Wang Yafan
Anna Blinkova → replaced by Liudmila Samsonova Danielle Collins → replaced by Francesca Di Lorenzo Coco Gauff → replaced by Viktoriya Tomova Madison Keys → replaced by 
Sara Errani
Barbora Krejčíková → replaced by Tereza Martincová Ann Li → replaced by 
Danka Kovinić Jessica Pegula → replaced by Clara Tauson
Rebecca Peterson → replaced by Christina McHale
Yulia Putintseva → replaced by 
Renata Zarazúa Anastasia Potapova → replaced by Stefanie Vögele Kristie Ahn Sloane Stephens → replaced by Natalia Vikhlyantseva| Country | Player | Country | Player | Rank1 | Seed | |
|---|---|---|---|---|---|---|
| Australia | Ellen Perez | Australia | Storm Sanders | 117 | 1 | |
| Kaitlyn Christian | Sabrina Santamaria | 123 | 2 | |||
| Japan | Japan | |||||
| Australia | Arina Rodionova | Rosalie van der Hoek | 167 | 4 |
The following pair received a wildcard into the doubles main draw:
The following pair received entry into the doubles main draw using a protected ranking:
The following pair received entry into the doubles main draw as an alternate:
Anna Blinkova / Lucie Hradecká → replaced by Elixane Lechemia / Ingrid Neel Misaki Doi / Nao Hibino → replaced by Linda Fruhvirtová / Tereza Martincová Coco Gauff / Caty McNally → replaced by Beatrice Gumulya / Jessy Rompies Makoto Ninomiya / Yang Zhaoxuan → replaced by Jamie Loeb / 
Erin Routliffe
