Introduction The objective of the present study was to evaluate the prevalence of hepatitis E virus in acute hepatitis in pediatric patients. Methods This was a cross-sectional study including 180 children with acute hepatitis. Blood samples were obtained and subjected to study the serological markers of hepatitis B surface antigen (HBsAg), hepatitis B core IgM (HBc IgM), hepatitis C IgG (HCV IgG) and hepatitis A IgM (HAV IgM), hepatitis E IgM and IgG, cytomegalovirus IgM (CMV IgM) and specific antibodies IgM for Epstein Barr virus by ELISA. Also ELISA attempted the laboratory diagnosis of autoantibodies by performing assay of antinuclear and anti-smooth muscle antibodies. Real time PCR was used for determination of HEV-RNA in samples positive for HEV serological markers. Results From a total of 180 children with acute jaundice 69.4% were males and 39.6% were females with mean age ± standard deviation 5.8±3.5 years. Positive HEV markers were found in 47 patients (26.1%). A comparison between demographic, clinical and laboratory findings in children with positive HEV markers and children negative for HEV markers, revealed significant association with contact of animals (p=0.001), rural residence (p=0.001), presence of positive autoantibodies (p=0.001) and positive HAV IgM (p=0.001). The markers of hepatitis E virus showed significantly higher prevalence in children below age of 6 years (p=0.04). Conclusions HEV infection is more common in preschool age. There is a significant association between contact with animals, rural residence and other hepatitis affection like autoimmune hepatitis and other viral hepatitis viruses such as hepatitis A.