The 2021 Open de Oeiras II was a professional tennis tournament played on clay courts. It was the second edition of the tournament, part of the 2021 ATP Challenger Tour. It took place in Oeiras, Portugal between 5 and 11 April 2021.
The following players received wildcards into the singles main draw:
The following player received entry into the singles main draw as a special exempt:
The following players received entry into the singles main draw as alternates:
The following players received entry from the qualifying draw: