However, Florence Welch stated that a vocal cord injury has left her unable to sing.
The singer took to Twitter and her official website to apologise to fans for missing out on the gigs.
She wrote: "I'm so sorry to all the fans, I was desperate to still perform, but was told without question not to, so as not to do permanent damage."
Benicassim organisers later confirmed the news, stating: "Given the sudden and unexpected illness suffered by Miss Welch, FIB 2012 organisation has been unable to find a substitute in such a small time frame."
It is expected that the reformed band At the Drive-In will move up the bill to take over Florence + the Machine's headline slot.
The event runs until July 15, and will also see performances from Bob Dylan, The Stone Roses and New Order.