At the start of the hostilities she was involved in the blockade of the Gibraltar Strait to prevent the rebel transport of troops from Spanish Morocco to southern Spain.

Since Lepanto was likely responsible for the fatal hit in the forward magazine that sank the enemy cruiser, she was awarded the Distintivo de Madrid along with other loyalist vessels.

The next day, Commander of the Fleet Miguel Buiza asked for political asylum and the ships were requisitioned by the French authorities and left in the custody by a few crewmen, the rest being held in a prison camp at Meheri Zabbens.

On 2 April 1939, just 24 hours after official end of the Civil War, Lepanto and her sister ships which had fought for the Republic sailed back to Spain with new Nationalist crews.

Participating in an antisubmarine warfare exercise on 27 July 1940, Lepanto operated in company with destroyers Alcalá Galiano and Churruca against submarines C2, C4, and General Mola.