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The main objective of the study was to identify factors influencing puerperal sepsis amongpost-partum women at Hoima regional referral hospital, in Hoima district, Western Uganda.The specific objectives were; To determine the prevalence of puerperal sepsis at Hoimaregional referral hospital, to assess the social demographic factors affecting puerperal sepsisat Hoima regional referral hospital, to determine Patients factors affecting puerperal sepsisat Hoima regional referral hospital and to determine the healthcare factors affecting theprevalence of puerperal sepsis at Hoima regional referral hospital. The study adopted thedescriptive cross-sectional method. The study population was all mothers in the maternityward of Hoima regional referral hospital who developed puerperal sepsis and consented tothe study. The two sets of data; qualitative and quantitative data were analyzed separatelyusing Microsoft Excel manually and interpreted into averages and percentages and presentedon tables, graphs, and pie charts. It was found that the prevalence of puerperal sepsis was37.5%, with most participants (51.7%) delivered by cesarean section, and 35.5% byspontaneous vaginal delivery. The study concluded that the majority of puerperal sepsisoccurs due to poverty, low income, and low maternal age and that the caesarian section is avery high-risk factor. The study further recommended that the government through theMinistry of Health should partner with hospitals creating affordable costs for motherswhenever serious conditions arise. Also, the promotion of education of girl children to higherlevels would reduce low maternal age and also directly reduce puerperal sepsis. Furthermore,healthcare workers should work in a skilled way to prevent sepsis in postpartum mothers.