December 5, 1859 |- | California(1) | | Henry P. Haun (D) | Interim appointee lost election to finish the termSuccessor elected March 5, 1860. | | Milton Latham (D) | March 5, 1860 |- | South Carolina(2) | | James Chesnut Jr. (D) | Withdrew November 10, 1860. | Vacant | Not filled this Congress |- | South Carolina(3) | | James H. Hammond (D) | Withdrew November 11, 1860. | Vacant | Not filled this Congress |- | Mississippi(2) | | Albert G. Brown (D) | Withdrew January 12, 1861. | Vacant | Not filled this Congress |- | Maine(1) | | Hannibal Hamlin (R) | Resigned January 17, 1861, to become Vice President of the United States.Successor elected January 17, 1861. | | Lot M. Morrill (R) | January 17, 1861 |- | Alabama(3) | | Benjamin Fitzpatrick (D) | Withdrew January 21, 1861. | Vacant | Not filled this Congress |- | Alabama(2) | | Clement C. Clay (D) | Withdrew January 21, 1861. | Vacant | Not filled this Congress |- | Florida(1) | | Stephen Mallory (D) | Withdrew January 21, 1861. | Vacant | Not filled this Congress |- | Florida(3) | | David L. Yulee (D) | Withdrew January 21, 1861. | Vacant | Not filled this Congress |- | Mississippi(1) | | Jefferson Davis (D) | Withdrew January 21, 1861. | Vacant | Not filled this Congress |- | Georgia(3) | | Alfred Iverson Sr. (D) | Withdrew January 28, 1861. | Vacant | Not filled this Congress |- | Kansas(2) | New seat | New state admitted to the Union January 29, 1861Senator was not elected until the next Congress. | Vacant | Not filled this Congress |- | Kansas(3) | New seat | New state admitted to the Union January 29, 1861Senator was not elected until the next Congress. | Vacant | Not filled this Congress |- | Georgia(2) | | Robert Toombs (D) | Withdrew February 4, 1861. | Vacant | Not filled this Congress |- | Louisiana(2) | | Judah P. Benjamin (D) | Withdrew February 4, 1861. | Vacant | Not filled this Congress |- | Louisiana(3) | | John Slidell (D) | Withdrew February 4, 1861. | Vacant | Not filled this Congress |- | Tennessee(2) | | Alfred O. P. Nicholson (D) | Withdrew March 3, 1861. | Vacant | Not filled this Congress