The Cathedral is home to two major instruments.  The West Gallery organ dates from 1907 and is the work of the Boston firm of Hutchings-Votey.  It boasts 51 ranks with more than 3,000 pipes.

The Archbishop Thomas J. Murphy Millennium Organ in the East Apse was completed in 2000.  It is the work of noted Los Angeles organ-builder Manuel Rosales.  The organ incorporates several ranks of pipes from the 1927 organ of Casavant Frères which served the Cathedral for more the seventy years.  This organ of 48 ranks of pipes was designed to complement the instrument in the West Gallery.  From the four-manual master console in the East Apse, the organist has complete control over the tonal resources of both the Rosales organ and the Hutchings-Votey.