The study describes a series of 12 critically ill adult patients with West Nile virus neuroinvasive disease (WNND) admitted to intensive care units in the Lazio region of Italy from July 1 to September 1, 2025. These patients comprised 6.1% of 197 persons with confirmed WNV infection, of whom 32% had WNND. Median age was 76.5 years, 75% were male; the most common symptoms included fever, muscle aches, gastrointestinal distress, confusion, limb weakness, and psychomotor retardation. Cerebrospinal fluid analysis showed lymphocytic pleocytosis (median 135 cells/mm³), elevated protein (median 126 mg/dL), and normal glucose; Brain MRI revealed T2/FLAIR hyperintensities in the thalamus and brainstem in most patients. Four patients had cardiac involvement, including two with suspected myocarditis and one with Takotsubo syndrome. Five patients (41.7%) died within 30 days, non-survivors were older (median 83 years) with multiple comorbidities.