The Harpoon missiles have a range of 50 nmi (93 km; 58 mi) at Mach 0.9 carrying a 227-kilogram (500 lb) warhead.

The vessels also mount a single OTO Melara 76-millimetre (3.0 in)/62 calibre naval gun capable of firing 85 rounds per minute up to 8.7 nmi (16.1 km; 10.0 mi) with each shell carrying a 6 kg (13 lb) warhead.

[1][a] For AAW defence, the ships mount a single Meroka 20 mm (0.79 in)/120 12-barrelled close-in weapons system (CIWS) capable of firing 3,600 rounds per minute up to 2 km (1.2 mi).

[4] As long-hulled versions of the Oliver Hazard Perry class, the Santa María-class frigates have twin hangars to accommodate up to two Sikorsky SH-60B Seahawk Light Airborne Multi-Purpose System (LAMPS) III helicopters though only one is usually embarked.

[4] In April 2019, the frigate was part of Standing NATO Maritime Group 2 operating in the Black Sea in support of Ukraine.

[6] On 8 October 2022 the ship suffered serious fire damage, mainly in the helicopter hangar (empty of aircraft at the time), while berthed at Rota, and delaying participation in the Operation Atalanta anti-piracy patrol off Somalia.

[7] On 15 December 2023, Santa María tracked the Kilo-class Russian submarine Ufa when the submersible sailed through Spain's Atlantic exclusive economic zone.