Isotopic and geochemical studies conducted on the Voisey’s Bay deposit, Labrador, Canada, suggest crustal contamination of the primary magma as a trigger for sulfur saturation and formation of the deposit. The use of multiple S isotopes has allowed for the identification of a bacterial sulfate reduction biosignature in the Tasiuyak gneiss in the footwall to the Voisey’s Bay deposit. This putative biosignature is preserved in the deposit even at high silicate magma/sulfide melt ratios (R-factor) and links the S present in the Voisey’s Bay deposit to the Tasiuyak gneiss. Iron isotopes in the Voisey’s Bay deposit have been reset to magmatic values at R-factors > ≈ 100, but S isotope data can be used to model higher R-factors. A contamination model results in calculated R-factors of 433 ± 177. The multiple S isotope data are a new proxy to directly link S from the deposit to crustal S sources even in deposits with high R-factors where the equilibration with large amounts of silicate magma can make interpreting a link between the deposit and the sulfur source difficult.