Last week the 23-time Grand Slam winner pulled out of the Madrid WTA event due to a fever.
The American tennis star made her comeback in February, six months after giving birth to baby Olympia, when she competed at Indian Wells and Miami, but has admitted she is struggling to get fully fit.
A statement on the tournament's Twitter feed read:
We are so sad to announce that @serenawilliams, a 4-time Champion in Rome, has withdrawn from #ibi18. ? Obviously we can't wait to see her again on Foro Italico's red clay, perhaps in 2019? ? pic.twitter.com/CnM8tTadhY
— Internazionali Bnl (@InteBNLdItalia) May 9, 2018
Williams has won the Rome title four times in 2002, 2013, 2014 and 2016.
Rome was also the city where she met her husband Alexis Ohanian, and also the city where he proposed.
Serena Williams celebrates her first Italian Open title in 2002. Photo: Gabriel Bouys/AFP
Williams, 36, will now be a doubt for the French Open in Paris from May 27th to June 10th. She has won the title three times, most recently in 2015.
She won the Australian Open while pregnant and returned in February alongside her sister Venus in a US Fed Cup first-round tie. She lost to Venus in the third round at Indian Wells and to Japan's Naomi Osaka at Miami.
If she were to make her Grand Slam comeback at Roland Garros, it would be without having played a match on clay since 2016.
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Photo: Tiziana Fabi/AFP