The etiological agent remained unidentified in a large number of patients hospitalized for acute encephalitis syndrome (AES) in 2008-2009 in Uttar Pradesh and Bihar, north India. All patients were found to present with fever and altered sensorium, while 28%, 19% and 13% showed hepatomegaly, splenomegaly and meningeal signs, respectively. Involvement mostly of children with abnormal hepatic features prompted us to undertake an exploratory study on viral hepatitis A to determine its association, if any, with hepatic derangements. AES patients (n = 2515) and healthy children (n = 167) were investigated for the presence of serum anti-hepatitis A virus (anti-HAV) IgM and anti-Japanese encephalitis (anti-JE) virus IgM by ELISA. Cerebrospinal fluids (CSFs, n = 595) and rectal swabs (n = 182) were examined for anti-HAV IgM and/or HAV RNA. Anti-HAV IgM was detected in the sera of 14.6% patients as against 6.6% of healthy children (p = 0.0042). Anti-JE virus IgM positivity was < 10% and 0%, respectively, among these groups. Anti-HAV IgM seropositivity was significantly high in patients with hepatomegaly and raised liver enzyme levels. Among anti-HAV IgM seropositive patients, CSF anti-HAV IgM positivity was detected in 56.9%, of which 18% had evidence of fecal excretion/viremia of HAV. CSF anti-HAV IgM positivity in AES patients was associated with pleocytosis and low glucose levels in CSF. The data of this study suggest association of HAV infection with increase in abnormal hepatic functions of AES patients and warrants enhanced hospital and community-based surveillance on hepatitis A for implementation of preventive measures to reduce the HAV infections and their impact on AES in north India.