Microbial sulfate reduction in oil reservoirs (biosouring) is often associated with secondary oil production where seawater containing high sulfate concentrations (~28 mM) is injected into a reservoir to maintain pressure and displace oil. The sulfide generated from biosouring can cause corrosion of infrastructure, health exposure risks, and higher production costs. Isotope monitoring is a promising approach for understanding microbial sulfur cycling in reservoirs, enabling early detection of biosouring, and understanding the impact of souring. Microbial sulfate reduction is known to result in large shifts in the sulfur and oxygen isotope compositions of the residual sulfate, which can be distinguished from other processes that may be occurring in oil reservoirs, such as precipitation of sulfate and sulfide minerals. Key to the success of this method is using the appropriate isotopic fractionation factors for the conditions and processes being monitored. For a set of batch incubation experiments using a mixed microbial culture with crude oil as the electron donor, we measured a sulfur fractionation factor for sulfate reduction of -30‰. We have incorporated this result into a simplified 1D reservoir reactive transport model to highlight how isotopes can help discriminate between biotic and abiotic processes affecting sulfate and sulfide concentrations. Modeling results suggest that monitoring sulfate isotopes can provide an early indication of souring for reservoirs with reactive iron minerals that can remove the produced sulfide, especially when sulfate reduction occurs in the mixing zone between formation waters containing elevated concentrations of volatile fatty acids and injection water containing elevated sulfate. In addition, we examine the role of reservoir thermal, geochemical, hydrological, operational and microbiological conditions in determining microbial souring dynamics and hence the anticipated isotopic signatures.