[2] On January 25, 1861, Gladden accepted appointment as lieutenant colonel of the 1st South Carolina Infantry Regiment, but soon resigned to become a member of the Louisiana secession convention.

[1][2] He was in command of his brigade during the bombardment of the Confederate forts at Pensacola harbor, and General Braxton Bragg expressed thanks for the able support Gladden provided.

[1][3][5] On the first day of the Battle of Shiloh, April 6, 1862, Gladden was mortally wounded by a shell fragment, which required amputation of an arm on the field.

[1][2][3] General P. G. T. Beauregard, commander of the Army of Mississippi after the death of General Albert Sidney Johnston at Shiloh on April 6, 1862, described Gladden's death as follows: "In the same quarter of the field all of Withers' division, including Gladden's brigade, reinforced by John C. Breckinridge's whole reserve, soon became engaged, and Benjamin Prentiss' entire line, though fighting stoutly, was pressed back in confusion.

We early lost the services of the gallant Gladden, a man of soldierly aptitudes and experience, who, after a marked influence upon the issue in his quarter of the field, fell mortally wounded.