We recently discovered a novel human pathogen closely related to Ehrlichia muris detected using PCR, culture, and serology in clinical specimens from Minnesota and Wisconsin (Pritt et al., N. Engl. J. Med. 2011). We now present our 5 years’ experience (2009-2013) of human infections with this bacterium. Blood from patients with suspected ehrlichiosis or anaplasmosis was tested using PCR targeting the Ehrlichia/Anaplasma GroEL Heat Shock Operon gene. Epidemiologic data was gathered using a standardized questionnaire. During 6/1/2009-8/19/2013, blood from 30 MN and 28 WI patients tested PCR positive for this new Ehrlichia sp. This result was also detected in residents from North Dakota (3), Indiana (1) and Michigan (1) with recent travel to WI or MN (total cases=63). Patient specimens (n=11,046) from 44 other states tested negative. The Ehrlichia sp. was cultured from the blood of one WI patient. Patients comprised 40 men and 23 women, ages 23 - 94 years (median=62 years). Among patients with available data, infection manifested with fever (53/60), headache (40/57), lymphopenia (16/28), and thrombocytopenia (28/43); 11 of 48 were hospitalized (3-15 days, median 4 days) and 55 received doxycycline treatment and made a full recovery, while one patient recovered without treatment. Treatment or outcome data were unavailable for 7 patients. Conclusion: The novel Ehrlichia sp. appears to circulate in a region where ehrlichiae have not historically been known to be endemic and causes a disease which is clinically similar to human monocytic ehrlichiosis due to E. chaffeensis and anaplasmosis due to Anaplasma phagocytophilum. These findings should be taken into consideration for diagnosis and surveillance in residents or individuals with travel to MN and WI states.