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Unfortunately for France, yellow fever decimated Napoleon's army of 30,000 troops in St. Domingue (Haiti) during its expedition. Similarly, ten years earlier, British troops suffered a similar fate on the island and had casualty rates as high as 70%. France was utterly unprepared to deal with yellow fever. Additionally, the war between France and England posed a serious threat to French ambitions in North America. The deadly outbreak of yellow fever ultimately ended Napoleon's North American dreams. He decided to give up his plans for Louisiana and surprised Monroe and Livingston the entire Louisiana territory for $15 million. Although this far exceeded their instructions from President Jefferson, they agreed.

When news of the sale reached the United States, the West was elated. President Jefferson, however, was in a quandary. He had always advocated strict adherence to the letter of the Constitution, yet there was no provision empowering him to purchase territory. Given the public support for the purchase and the obvious value of Louisiana to the future growth of the United States, Jefferson decided to ignore the legalistic interpretation of the Constitution and forgo the passage of a Constitutional amendment to validate the purchase. This decision contributed to the principle of implied powers of the federal government.