The authors describe two of three cases of West Nile virus (WNV) meningoencephalitis admitted to ICU in Ferrara (south of Po River) underlying the main common features. They focus on the difficulties in diagnosis, with key-points including seasonality (late summer in Italy), unspecific flu-like symptoms at the beginning, as hyperpyrexia, myalgia and asthenia, followed by neurological impairment, and use of steroids in the patient clinical history. Special attention is deserved to the poor outcome at both short and long term.