USS Santee (1855) was a wooden-hulled, three-masted sailing frigate of the United States Navy. She was the first US Navy ship to be so named and was one of its last sailing frigates in service. She was acquired by the Union Navy at the start of the American Civil War, outfitted with heavy guns and a crew of 480, and was assigned as a gunship in the Union blockade of the Confederate States of America. She later became a training ship for the U.S. Naval Academy.
Rated at 44 guns, she was laid down in 1820 by the Portsmouth Navy Yard, but due to a shortage of funds, she long remained uncompleted on the stocks. She was finally launched on 16 February 1855, but not commissioned until 9 June 1861, Captain Henry Eagle in command.
Santee departed Portsmouth, New Hampshire on 20 June 1861, stopped at Hampton Roads, Virginia to load ammunition, and resumed her voyage to the Gulf of Mexico on 10 July.
On 8 August, the frigate captured the schooner C. P. Knapp in the gulf some 350 miles south of Pensacola and escorted the blockade runner to that port. On 27 October, Santee took her second prize, Delta, off Galveston; the hermaphrodite brig had attempted to slip into Galveston with a cargo of salt from Liverpool.