Villeneuve came out of Cadiz in late 1805, and was engaged by Nelson in the decisive Battle of Trafalgar on 21 October. During the battle "Neptune" fired on Nelson's flagship, , and duelled with several British ships including , and . As the British began to overwhelm the combined fleet, the relatively undamaged "Neptune" joined several ships in a retreat to Cadiz. She sortied again two days later in an attempt to recover some of the prizes, but the fleet lost more ships than they regained, and "Neptune" had to be towed back to harbour. There she remained, under a close British blockade, until the Spanish declared war on the French. Trapped in the port, the French handed their ships over to the Spanish, who renamed "Neptune" "Neptuno", replacing a Spanish ship lost at Trafalgar. "Neptuno" served with the Spanish for a further 12 years, being broken up in 1820.