We report the occurrence of concurrent infections with multiple acute febrile illness (AFI) pathogens during an ongoing prospective laboratory-based surveillance in four infectious disease hospitals in urban and rural areas of Egypt from June 2005 to August 2006. Patients were screened for Leptospira, Rickettsia typhi, Brucella, or Salmonella enterica serogroup Typhi by various methods including serology, culture, and PCR. One hundred eighty-seven of 1,510 patients (12.4%) evaluated had supporting evidence for the presence of co-infections; 20 (1%) of these patients had 2 or more pathogens based upon confirmatory 4-fold rise in antibody titer, culture, and/or PCR. Most coinfected patients lived or worked in rural agricultural areas. The high coinfection rates suggest that defining the etiologies of AFI is imperative in guiding proper disease treatment, prevention, and control strategies in Egypt.