We treated a patient simultaneously infected with hepatitis E virus and Leptospira interrogans, both acquired in China. Severe hyperbilirubinemia required nearly 200 days to resolve, transminase elevation showed a fluctuating course, and liver biopsy specimens showed fibrosis unusual for hepatitis E. Leptospirosis appeared to have altered the course of hepatitis E virus infection in this patient, even though infection with Leptospira was cleared with antibiotics by 50 days after the onset of the hepatitis symptoms.