Abstract Invasive Burmese pythons (Python bivittatus) in the Everglades of Florida, United States, have drastically reduced populations of mammals, yet populations of some rodents appear unaffected by the invasion. To understand this pattern, we radio-tagged cotton rats (Sigmodon hispidus) in areas of high and low python occurrence densities (hereafter occurrence) and quantified the effects of python occurrence, seasonality, and sex on their survival and cause-specific mortality. Cotton rat survival was not influenced by difference in python occurrence (hazard ratio = 1.32, 95% CI = 0.77–2.26, P = 0.30). However, cotton rats were at greater risk from mortalities caused by mammals in areas of low python occurrence. In areas with elevated python occurrence, we attributed most cotton rat mortalities to birds of prey (48.6%) and reptiles (non-python = 24.3%, python = 16.2%). Where python occurrence was relatively low, we attributed cotton rat mortalities to native reptilian (28.6%), avian (35.7%), and mammalian predators (35.7%) with no python-related deaths. In total, pythons were responsible for 11.8% of all cotton rat mortalities. Finding no difference in the survival of cotton rats, despite differences in the causative agents of mortality, suggests that predation pressure from an invasive predator was compensatory for cotton rat population dynamics. This type of compensatory mortality is common for small mammals and helps explain why mammal communities in python-invaded portions of the Greater Everglades Ecosystem are increasingly dominated by cotton rats and other rodents.