Mr Flores, 56 had been in a coma since undergoing emergency surgery.
He had been under house arrest on charges of embezzlement and illegal enrichment. Mr Flores handed himself in to the authorities in September 2014.
He was accused of diverting a large part of a donation of $15m given by Taiwan to help the victims of earthquakes in El Salvador in 2001.
Prosecutors say he misappropriated $5m and transferred it to his private bank account. Another $10m is alleged to have gone into his party's coffers.
Mr Flores, from the conservative Arena party, said that El Salvador enjoyed "a privileged relationship" with Taiwan because it backed the Asian country's request for membership of the United Nations.
Francisco Flores took office in 1999 and was in power until 2004.
Correspondents say many people in El Salvador had been encouraged that their country had begun to effectively fight high-level corruption when they saw attempts to bring Mr Flores to justice.
The former president of El Salvador, Francisco Flores, has died after suffering a brain haemorrhage.