Williams was beaten 6-2 6-4 by fellow wild card Kaitlin Quevedo in the opening round on Tuesday for her 10th straight singles loss after she returned from a 16-month break midway through last season.
The seven-times Grand Slam singles champion will need a wild card to feature at Roland Garros.
"Yeah, I mean, to get my feet dirty, this was a great start," Williams, 45, told reporters.
"I'm not able to play Rome, I have other commitments, unfortunately, so I'm really super sad about that, actually.
"My husband is Italian, so we feel sad that we can't be there. So we would love to keep it going on the clay."
Williams' last match on clay before Madrid was at the French Open in 2021 and she said she was happy with how she performed.
"I felt like in the last game I started to move better on the clay. But then it was the last game," she added.
"All these things take adjustments. I started my practice on clay a couple weeks after Miami. I haven't really played on clay in years. But I enjoy the clay, it's fun.
"I played against a very inspired opponent today."
The French Open begins on May 24.