World No.1 has withdrawn her name citing a right shoulder injury.
She had the chance of adding the first WTA 1000 event of the clay season to her rapidly growing trophy cabinet.
The 20-year-old Polish star is riding a 23-match win streak after winning her fourth consecutive title at the Porsche Tennis Grand Prix.
Her win on indoor clay came after becoming the first player to win the first three WTA 1000 events of the season at the Qatar Total Open, BNP Paribas Open, and Miami Open.
The Pole was set to play as the tournament’s top seed in Madrid and was due to open her tournament on Friday against a qualifier.
Swiatek will speak to reporters in Madrid on Wednesday to expound on her decision.
The Madrid Open is the first WTA 1000 event of the clay season and the main draw play begins on Thursday with qualifiers already underway.
Swiatek’s absence should not take away from a loaded women’s bracket with the likes of Indian Wells finalist Maria Sakkari, wildcard entrant Naomi Osaka, Aryna Sabalenka, and Garbine Muguruza all set to feature.