Santamaria died on Wednesday in Singapore at the his Marina Bay restaurant named Santi, said Ruben Mallat, manager of the three-star restaurant El Raco de Can Fabes in Barcelona. Mallat said the cause of death was not immediately unknown.
One of a generation of chefs who brought Spanish cuisine to the attention of international gourmets, Santamaria prided himself on using natural, seasonal ingredients to make Mediterranean-style dishes.
Born in Sant Celoni, outside Barcelona, Santamaria opened Can Fabes in 1981. By 1994, the restaurant had become the first in Spain to attain three Michelin stars. He owned three other restaurants in Spain which also garnered Michelin stars.
Author of some 10 books on cooking, Santamaria was awarded Spain's National Gastronomy Prize in 2009.
He clashed with Spanish culinary guru Ferran Adria and other chefs who brought high-tech methods to Spanish cuisine, arguing they used the same potentially unhealthy additives as hamburger joints. The criticism came to a head when he published his book "La Cocina al Desnudo" (The Naked Kitchen) in 2008.
Back then an international association of chefs, called Euro-toques, which 3,500 members from 18 countries, including 800 in Spain that also included Adria, issued a statement accusing Santamaria of trying to gain publicity and alarming consumers unnecessarily. It said the additives used in Adria-style cooking were legal and safe.
Santimaria shot back, demanding that chefs specify what ingredients they use.
Funeral arrangements were not immediately made known.