After a dangerous final voyage back from Haiti, Columbus landed back in Spain on 7 November, 1504. Queen Isabella of Castile was gravely ill, and soon she died, on November 26, 1504.
Weakened by rheumatism, exposure, and years of bad food Columbus had become very ill from his last trip, and he spent many months in Seville recuperating at the Monastery of Las Cuevas. On his first voyage he noted the "sore eyes" that later disabled him. He may have contracted malaria and typhus, and probably suffered from Reiter's syndrome, which combines eye and urinary tract disorders with arthritis.
Over the next year and a half, until his death, Columbus tried to regain his lost titles of Governor and Viceroy. He petitioned the crown and when he was well enough, followed the court of King Ferdinand to several cities in Spain hoping to see the king. In May, 1505, King Ferdinand finally granted Columbus an audience to present his claims to the riches of the Indies. His titles (Governor and Viceroy) were not returned, but the king did allow arbitration on his financial claims. The Admiral’s share was confirmed at ten percent of the royal one-fifth (the quinto real). This amounted to two percent of the riches of the Indies, a considerable amount, and it afforded the Columbus family a noble life style. Considering his poor health, it is apparent that concern over profits and rights was not for himself but for his sons Diego and Ferdinand. The Columbus family’s struggle for justice continued well beyond the Admiral’s death.
In late 1505, Columbus became too ill to travel any more and remained until his death in a modest house at Valladolid. He began to write his Book of Prophecies, a compilation of apocalyptical religious revelations. In the spring of 1506, at age 55, Columbus complained, "This illness now works me without pity." Cardiac complications had probably set in; his body was swollen with dropsy. The end was near. He ordered Diego to "provide for Beatriz Enriquez, mother of my son Don Ferdinand, so that she might live decently, as a person to whom I am greatly indebted."
On May 20, 1506, both sons, brother Bartolomeo and his friend Diego Méndez were at his side when the Admiral murmured "Into thy hands, O Lord, I commit my spirit" and passed away. His body was buried initially in Valladolid but then moved to several venues in Spain and the Indies before finally reaching the Cathedral of Seville.
Christopher Columbus Life - 1492 till his death