The Chapel of Santíssimo, to the left of the chancel, was completely redone between 1707 and 1708, remaining with the current configuration of plant centered with its sides formed by semi-circles, illuminated by upper lantern. The silver altarpiece inside it dates back and was built in several phases between 1632-1647 and represents a fundamental work of Portuguese jewelery, the work of master goldsmiths from Lamego and Porto. It consists of four floors, decreasing in height, topped by the figure of Jesus Christ. On each floor there are low reliefs with biblical themes. The stool is later, and was executed by Manuel Francisco and the assembler Gonçalo Pereira. The pilasters that support the arch and frame the altarpiece are from the second half of the 19th century.

At the time of the French Invasions, this work was saved due to an ingenious ploy by a diligent sacristan of the Cathedral, covering it entirely with plaster. Junot's troops entered the Porto Cathedral in 1807, plundering all the silver from the altars except for this monumental altarpiece.