"It is with great sadness that we announce the passing of our beloved Sinead. Her family and friends are devastated and have requested privacy at this very difficult time," RTE quoted a statement from the singer's family as saying.
Brash and outspoken - her shaved head, pained expression and shapeless wardrobe a direct challenge to popular culture's long-prevailing notions of femininity and sexuality - O'Connor changed the image of women in music in the early 1990s.
She crashed onto the global music scene at the beginning of the decade with her mesmerising version of the song originally written by Prince, facing directly into the camera for the music video that has subsequently been viewed almost 400 million times on YouTube.
Known as much for her outspoken views on religion, sex, feminism and war as for her music, she will be remembered in some quarters for ripping up a photo of Pope John Paul II during a television appearance on Saturday Night Live.
"Everyone wants a pop star, see?" she wrote in her 2021 memoir Rememberings.
"But I am a protest singer. I just had stuff to get off my chest. I had no desire for fame."
O'Connor converted to Islam in 2018 and changed her name to Shuhada Sadaqat although she continued to perform under the name Sinead O'Connor.
"Her music was loved around the world and her talent was unmatched and beyond compare," Irish Prime Minister Leo Varadkar posted on Twitter, sharing his condolences with "all who loved her music".
