Aerobic composting is a common management practice to inactivate pathogens in manure; however, additional research on the role of compost composition in pathogen inactivation is needed. The objective of this study was therefore to determine the effect of the carbon:nitrogen (C:N) ratio and the presence of ammonium sulfate on inactivation of Salmonella spp. in cow manure-based mixtures composted in a bioreactor under controlled conditions. Compost preparations with an initial C:N ratio of 20:1 required a maximum of 4 days of storage before Salmonellae were inactivated by 7 log10, whereas preparations with C:N ratios of 30:1 and 40:1 C:N required more than 5 and 7 days of storage, respectively. The pH values of both the 20:1 and 30:1 C:N preparations decreased during the onset of composting before increasing to >8. In contrast, pH values of 40:1 C:N preparations increased immediately to >8, generally within the first day of storage. Maximum temperatures observed in 20:1 C:N preparations for inactivation of pathogens were less than 50 °C, and the cumulative heat exposure required for pathogen inactivation in 20:1 C:N preparations was 15-fold less than in 40:1 C:N preparations. Supplementation of compost mixtures with 0.08% ammonium sulfate resulted in slightly higher temperatures; however, these higher temperatures did not translate into more rapid rates of pathogen inactivation.