She set sail on her final voyager on 18 February 1770, departing Cadiz under the command of Captain Joseph Antonio de Alzaga, with Joseph de Zavalsa as Master and Manuel de Buenechea as pilot. On 25 July she was sighted by the "Gallardo", whose captain, Juan Esteban de Ezpeleta (es), knew de Alzaga. The "Gallardo" signalled to her with a cannon shot, but it went unanswered. The first officer of the "Gallardo", Joseph de Alvarez, was sent to investigate and found that the "Oriflama" had been swept by a mysterious plague. Half the crew had already died, and the rest were dying, with only thirty men barely able to haul a sail.