From April 2009 onwards Blas de Lezo, along with other vessels of SNMG-1, participated in NATO's Allied Protector operation to combat piracy in the waters of the Gulf of Aden and the Horn of Africa.

On 4 July 2009 during the course of an operation, the crew boarded two vessels suspected of piracy after receiving a warning from the Liberian merchant United Lady of a possible attack.

She was joined by the aircraft carrier USS Dwight D. Eisenhower, a Ticonderoga-class cruiser, and three Arleigh Burke-class destroyers with which she trained.

On 11 June 2013 Blas de Lezo sailed from the Naval Station of Rota to take command of NATO Permanent Group No.

On 29 August 2013 she departed for the port of Málaga to start the second phase of her deployment which included the participation on the international exercise Brilliant Mariner 2013.

[citation needed] On 11 July 2014 the frigate Cristóbal Colón returned from Operation Atalanta while the remaining four ships of the F-100 class were based in Ferrol.

On 22 January 2022, amid the Russo-Ukrainian crisis, Blas de Lezo left Ferrol to join the Standing NATO Maritime Group 2, expected to be deployed in the Black Sea.