2021 San Marino Open – Singles

Adrian Ungur was the defending champion when the event was last held in 2014 but chose not to defend his title as he had retired from professional tennis.

Holger Rune won the title after defeating Orlando Luz 1–6, 6–2, 6–3 in the final.

Seeds
• # 🇮🇹 Marco Cecchinato (semifinals)

• # 🇫🇷 Gilles Simon (second round)

• # 🇮🇹 Salvatore Caruso (second round)

• # 🇧🇴 Hugo Dellien (semifinals)

• # 🇮🇹 Federico Gaio (first round)

• # 🇦🇷 Tomás Martín Etcheverry (withdrew)

• # 🇦🇷 Sebastián Báez (first round)

• # Blaž Rola (second round)