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This study aimed to compare the epidemiology of Rickettsia felis infection and malaria in France, North Africa, and sub-Saharan Africa and to identify a common vector. Blood specimens from 3,122 febrile patients and from 500 nonfebrile persons were analyzed for R. felis and Plasmodium spp. We observed a significant linear trend (p<0.0001) of increasing risk for R. felis infection. The risks were lowest in France, Tunisia, and Algeria (1%), and highest in rural Senegal (15%). Co-infections with R. felis and Plasmodium spp. and occurrences of R. felis relapses or reinfections were identified. This study demonstrates a correlation between malaria and R. felis infection regarding geographic distribution, seasonality, asymptomatic infections, and a potential vector. R. felis infection should be suspected in these geographical areas where malaria is endemic. Doxycycline chemoprophylaxis against malaria in travelers to sub-Saharan Africa also protects against rickettsioses; thus, empirical treatment strategies for febrile illness for travelers and residents in sub-Saharan Africa may require reevaluation.