Encephalitis is a severe neurological syndrome associated with high morbidity and mortality as well as long-term neurological sequelae. Despite being an important public health problem, very few extensive population-based studies were conducted so far in the world and none in Central Europe. Altogether 114 consecutive patients meeting the initial criteria for encephalitis were enrolled at the Warsaw Hospital for Infectious Diseases between June 2012 and July 2015. Eighteen patients were secondarily excluded from the analysis due to incomplete data or noinfectious cause. Potential pathogen sequences were searched for by molecular methods in the cerebrospinal fluid (CSF) and specific antibodies were detected in CSF and sera. An infectious agent was identified in 41 patients (42.7%). The most frequently diagnosed infections were Human herpesvirus 1 (HHV-1) (22 cases, 24%) followed by Enterovirus (6 cases, 6.3%), Varicella zoster virus (VZV) (5 cases, 5.2%), Tick-borne encephalitis virus (TBEV) (6 cases, 6.3%) and Cytomegalovirus (CMV) (2 cases, 2.1%). There were no cases of human adenovirus, Human herpesvirus 6 (HHV-6) or West Nile virus (WNV) infection identified. In 55 cases (57.3%) the cause of encephalitis remained unknown. Compared to patients in whom the diagnosis was determined the latter group contained more women, was less likely to manifest fever and had lower CSF pleocytosis (p < 0.05) In summary, we identified HHV-1 followed by Enterovirus, VZV and TBEV as the most common causes of encephalitis among adult patients in Poland. In a large proportion of patients the cause of encephalitis remained unknown.