Background Typhoid fever, despite being preventable, places a significant burden on low- and middle-income countries. Although understanding of the global burden of typhoid fever is improving, evidence on the economic burden of typhoid fever remains limited. This study estimated the cost of illness associated with typhoid fever in the Kisantu Health Zone of the Democratic Republic of the Congo. Methods A standardized patient-level survey was conducted to estimate the cost of illness associated with typhoid fever. Patients with typhoid fever were recruited from eight health centers and one hospital. Multiple interviews were conducted to capture the full costs incurred throughout the illness episode. Results From March 2022 to March 2025, among 140 enrolled patients, 91 were classified as mild cases and 49 as severe cases with suspected intestinal perforation/peritonitis. The mean cost of illness for typhoid fever was US$ 108 (95% CI: US$ 90-127) for mild cases and US$ 579 (95% CI: US$ 506-663) for severe cases, indicating that costs for severe cases were more than five times higher than those for mild cases. All direct medical costs were paid out-of-pocket by patients, and no patients were covered by insurance or government subsidies. Conclusions Typhoid fever imposes a substantial economic burden in the Democratic Republic of the Congo. These findings provide important evidence for evaluating the economic value of typhoid conjugate vaccine introduction in high-burden settings.