The giant mid-Miocene Cerro de Pasco Cordilleran polymetallic (Zn-Pb-Ag-Cu-Bi) deposit in central Peru formed during three successive mineralization stages resulting in low- to high-sulfidation mineral associations emplaced at a paleodepth from <500 to 1,500 m: (1) pyrrhotite pipes grading outward to sphalerite and galena replacement bodies (stage A), (2) deep quartz-pyrite veins (stage B1) and a funnel-shaped massive replacement body of pyrite-quartz (stage B2) with quartz-sericite ± kaolinite alteration, and (3) well-zoned Zn-Pb-(Bi-Ag- Cu) carbonate-replacement orebodies (stage C1) and E-W–trending Cu-Ag-(Au-Zn-Pb) enargite-pyrite veins (stage C2); stages C1 and C2 are accompanied by advanced argillic alteration. Field evidence indicates that the epithermal polymetallic mineralization has formed in the shallow part of a porphyry system.A detailed microthermometric and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) study of fluid inclusions hosted in gangue and, using near-infrared microscopy, opaque ore minerals from the different mineralization stages as well as available bulk and in situ secondary ion mass spectrometry (SIMS) stable isotopic data allow reconstruction of the evolution and tracing of the source(s) of the mineralizing fluids. Fluid inclusions are two phase (L + V), homogenize to liquid at moderate temperatures (~220°–280°C in stages A, B1, B2, and C2 and down to 150°C in stage C1), and show a wide salinity range (1.2–19 wt % NaCl equiv) with no evidence of phase separation. Fluids during mineralization stages A, B1, B2, and C1 are the result of mixing between a moderate-salinity metal-rich magmatic fluid and a low-salinity fluid at the (shallow) site of deposition. The moderate-salinity metal-rich magmatic fluid cannot be interpreted as an evolved intermediate-density fluid or its boiling product due to its salinity (up to 19 wt % NaCl equiv), its high base metal concentration (>1 wt % Mn, Fe, Zn, and Pb), and its high Li, B, As, and Sb contents (up to several thousands of ppm). The obtained results suggest that the moderate-salinity metal-rich magmatic fluid results from mixing at depth between metal-rich hypersaline fluids and low-salinity magmatic fluids exsolved late in the lifetime of the magmatic-hydrothermal system. The moderate-salinity metal-rich magmatic fluid resulting from this deep mixing rose to the epithermal environment, where it in turn mixed with low-salinity fluids that were stored below the paleowater table and had similar temperatures to the moderate-salinity fluid. In contrast, enargite-pyrite veins of stage C2 were formed by the ascent of CO2-bearing, contracted vapor-like fluids that subsequently mixed with cold meteoric water. No interaction with the moderate-salinity, metal-rich magmatic fluids has been registered in stage C2.The similarity between fluid compositions and evolution during stages A, B1, B2, and C1 contrasts with their significantly different mineral assemblages that are rather controlled by changing fO2, pH, fS2, and temperature. Trace element LA-ICP-MS analyses of sphalerite, pyrite, and enargite also reveal important compositional differences. The trace elements in the measured minerals reside to a significant extent in micro- to nanoscale solid sulfide and/or sulfosalt inclusions. A direct correlation between fluid composition recorded in the studied fluid inclusion assemblages and the measured trace element composition of sphalerite, pyrite, and enargite has not been found in most cases.The cyclic rise of metal-rich, moderately saline fluids that issued from dilution of hypersaline fluids stored at depth by low-salinity magmatic fluids is a major process in the formation of stages A, B1, B2, and C1 of the giant epithermal polymetallic deposit of Cerro de Pasco. Such a mechanism may also explain moderate-salinity fluids (≈20 wt % NaCl equiv) recorded in other magmatic-related polymetallic epithermal deposits worldwide.