Results of sulfur and oxygen isotope studies of sedimentary exhalative (SEDEX) Zn-Pb(-Ag-Au-Ba-F) deposits hosted in metamorphosed Paleozoic clastic and carbonate rocks of the Nome Complex, Seward Peninsula, Alaska, are consistent with data for similar deposits worldwide. Stable isotopic studies of the Nome Complex are challenging because the rocks have undergone Mesozoic blueschist- and greenschist-facies metamorphism and deformation at temperatures estimated from 390–490 °C. Studies of sulfur and oxygen isotopes in other areas suggest that, in the absence of chemical and mineralogical evidence for metasomatism, the principal effect of metamorphism is re-equilibration between individual minerals at the temperature of metamorphism, which commonly leads to a narrowing of the overall range of isotope values for a suite of rocks, but generally does not significantly modify the average whole rock value for that suite. Sulfur isotope studies of the stratabound and locally stratiform sulfide lenses at the Aurora Creek-Christophosen deposit, which is of possible Late Devonian-early Carboniferous age, show a large range of δ34Ssulfide values from -9.7 to 39.4‰, suggesting multiple sulfur sources and possibly complex processes of sulfide formation that may include bacterial sulfate reduction, thermochemical sulfate reduction, and Rayleigh distillation. Low δ34S values probably represent bacterial sulfide minerals remobilized from the host metasedimentary rocks either during the original seafloor mineralization or are related to a Cretaceous mineralizing event that produced Au-vein and base-metal replacement deposits; the latter process is supported by Pb isotope data. The Wheeler North deposit is similar to Aurora Creek-Christophosen but does not have negative δ34S values. It also probably formed in an euxinic sub-basin. The stratabound Nelson deposit, and the deformed veins at the Galena and Quarry deposits, may be older than the Aurora Creek-Christophosen and Wheeler North deposits. The Nelson deposit has a lower and narrower range of δ34S values (1.9 to 10.4‰), averaging about 8‰. The Galena and Quarry veins display δ34S values that are similar to those of the stratabound Nelson deposit. Barite samples from the Aurora Creek-Christophosen, Wheeler North, and Quarry deposits have 34S-enriched δ34S values between 25 and 30‰ that are consistent with derivation of the sulfur from coeval (Paleozoic) seawater sulfate. Given their δ34S values, it is likely that the Aurora Creek-Christophosen and Wheeler North deposits formed in closed sub-basins with euxinic conditions that led to extreme Rayleigh distillation to produce the very large range and very high δ34S values. The Nelson deposit probably formed within an anoxic but not euxinic sub-basin. At Nelson, sulfide was likely derived by a subsurface thermochemical sulfate reduction (TSR) reaction, similar to reactions that are inferred to have produced the sulfides in the Galena and Quarry deposits, which are interpreted as feeder veins for the stratabound deposits. Calculations of oxygen isotope temperatures are based on the assumption that evolved seawater with δ18O of 3‰ was the mineralizing and altering fluid related to the formation of the sulfide deposits. Temperatures of aluminous alteration and sulfide mineralization were between 109 and 209 °C, determined on the basis of oxygen isotope fractionations between the mineralizing fluid and proportionate amounts of quartz and muscovite in the rocks. These temperature estimates agree well with known temperatures of SEDEX mineralization worldwide. Sulfur isotope values also are generally consistent with the known ranges in SEDEX deposits worldwide (δ34S ≈ -5 to 25‰).