Assigned the duty of protecting American commerce in Cuban waters against the possible incursions of French warships or privateers during the "Quasi War" with France, Warren set sail for Havana, Cuba, on 31 December 1799, escorting the schooner Trio.

As the ships stood out of Nantasket Roads, near Boston, Massachusetts, Sailing Master Joseph Whitmore, in Warren, penned fervently in his journal, "God send us safe to our orders End in our Lawfull (sic) Ways in supporting our Independence.

[4] After a week at sea, Warren returned to Havana on 20 February 1800 and waited for a fleet of merchantmen to emerge from the harbor and form a convoy.

That evening, a dozen ships sailed, and Warren joined them as they emerged from the harbor and gave them routing instructions as they headed for the United States.

Warren joined man-of-war USS Ganges and a convoy of 22 merchantmen on 21 April 1800 and sailed with them for a time before returning to Havana early in May 1800.

On 24 June 1800, the ship's doctor sent Quarter Gunner William Dogget ashore to the hospital at Havana, the man suffering from a fever—later determined to be yellow fever.

During Warren's stay at Havana, her crew — hitherto "in general, healthy, and robust"[3] — began to have "evident symptoms of an increasing universal debility.

"[3] Warren, departing Havana in company with the frigate USS General Greene and 12 merchantmen, sailed for Veracruz, Mexico, on 26 June 1800.

Warren ultimately departed Veracruz on 23 July 1800, having had an average of 20 to 24 sick men ashore in the hospital and 25 on board unfit for duty.

Lieutenant Joseph Strout then took command and took the ship northward, bound for the United States leaving Havana on 17 August, crew very sickly.

[5] Meanwhile, as Warren sailed homeward, Secretary of the Navy Stoddert ordered Captain James Barron to take command of the ship as soon as possible after she arrived, with expressed instructions to "relieve the sick; recruit men to fill the deficiency; cleanse, reprovision, rewater, and prepare her for another cruise with the most dispatch.

In a letter dated 20 February, 1801 to Josiah Parker, Chaiman of the Committee on Naval Affairs, Navy Secretary Stoddert recommended selling her.