This prospective observational study aimed to identify what proportion of patients presenting to Waikato Hospital with undifferentiated symptoms of an acute febrile illness (USFI) have leptospirosis or murine typhus infection, and to identify factors at presentation predictive of each infection. It also aimed to identify infecting rickettsial organism(s) causing murine typhus in the region.Between 15/10/2009-15/10/2010 all adult patients presenting with USFI of greater than and equal to 72 hours with no clear diagnosis on presentation were invited to participate in the study. A structured questionnaire and examination were administered and acute and convalescent serology was performed. For patients returning positive murine typhus serology, rickettsial PCR analysis was performed on stored acute blood samples.Fifty-seven patients were recruited. Nine were diagnosed with leptospirosis, five with murine typhus, three with Epstein-Barr virus (EBV), two with cytomegalovirus (CMV), five with bacterial sepsis and six with other diagnoses. Twenty seven had an acute febrile illness for which no diagnosis was found. A low platelet count (p<0.001) was associated with murine typhus infection, and rural occupation (p<0.001) and a low lymphocyte count (p=0.001) with leptospiral infection. There was a trend towards rural residence being associated with murine tyhpus infection (p=0.059). Two of four patients with positive murine typhus serology returned positive PCR analysis for Rickettsia typhi.A significant proportion of patients presenting to Waikato Hospital with USFI had leptospirosis or murine typhus infection. A low platelet count and rural residence were associated with murine typhus infection, and rural occupation and a low lymphocyte count with leptospiral infection. R. typhi was identified as a rickettsial organism causing rickettsial fever in the Waikato region.