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Reactivated a little more than a year later, Vincennes spent the next three years suppressing the slave trade off Africa. After this hot, grueling period came yet another decommissioning. With the outbreak of hostilities between the States, Vincennes was promptly put into service by June 1861. She was assigned blockading duties with the Gulf Squadron off the Mississippi coast.

In one confrontation with Confederate blockade runners, Vincennes was run aground. Perhaps as a sign of the Vincennes spirit, the ship refused to explode when a slow match was put to her magazines to prevent her from falling into enemy hands. The ship was re-floated and later assumed command of a blockade at Ship Island, Mississippi, on October 4, 1862. Vincennes remained in the Mississippi Sound for the duration of the war and was finally taken out of service at the Boston Navy Yard in Massachusetts on August 28, 1865.

On October 5, 1867, more than 41 years after entering Naval service, the sloop-of-war Vincennes was sold at public auction for approximately $5,000.00

See Lieutenant Charles Wilkes' Biography.