The 2021 Sibiu Open was a professional tennis tournament played on clay courts. It was the tenth edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in Sibiu, Romania between 27 September and 3 October 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Italy | Stefano Travaglia | 98 | 1 | |
 Moldova, Republic of | Radu Albot | 104 | 2 | |
 Slovakia | Alex Molčan | 118 | 3 | |
 Bosnia and Herzegovina | Damir Džumhur | 129 | 4 | |
 Czech Republic | Zdeněk Kolář | 149 | 5 | |
| Marc-Andrea Hüsler | 159 | 6 | ||
 Australia | Thanasi Kokkinakis | 183 | 7 | |
 India | Sumit Nagal | 185 | 8 |
The following players received wildcards into the singles main draw:
Victor Vlad Cornea Vlad Andrei DancuThe following players received entry from the qualifying draw:
Yan Bondarevskiy David Ionel
Yshai Oliel Ștefan PaloșiThe following player received entry as a lucky loser:
See main article: 2021 Sibiu Open – Singles.
Stefano Travaglia def. Thanasi Kokkinakis 7–6(7–4), 6–2.See main article: 2021 Sibiu Open – Doubles.
Alexander Erler / Lucas Miedler def. 
James Cerretani / Luca Margaroli 6–3, 6–1.