The whites destroyed most of them in no time – European diseases such as small pox and yellow fever were fatal as the Indians had no immunity against them. They were forced to start paying taxes and were eventually forced into slavery, along with Africans who were brought over to the island. The Indians all died out in the end, while the Africans continued to work the sugar plantations and mines.

Cuba was a very strategic base to have in the area for the Spaniards, who organized their expeditions from there and continued exploiting the mines and other agricultural production, including sugar, tobacco and coffee. The island was a frequent target for raids and invasions by buccaneers and pirates from other sea-faring nations, particularly Great Britain and France, given its ideal location and abundant trade. Spain was very strict in regard to trading and prevented the colony from trading with others, so much so that a tobacco monopoly was established for a time, by which only trade with Spain was permitted. These restrictions were slackened in 1818 in response to local pressure, and the colony was allowed to start trading with the world.