Sanha died at at Val-de-Grace Hospital, where he was receiving treatment, CNN reported.
Sanha became president in September 2009, several months after President Joao Bernardo Vieira was assassinated. Sanha was interim president and then defeated another former president, Kumba Yala, in a runoff.
Since gaining independence from Portugal in 1974, Guinea-Bissau's history has been marked by coups and near-coups, which savaged the nation's infrastructure and economy, making it one of the poorest countries in the world.
The CIA Factbook lists Guinea-Bissau as an increasingly important weigh station for cocaine shipments from South America to Europe, CNN said.