Encephalitis is an inflammatory process involving the brain parenchyma associated with neurologic dysfunction. The main causes of infectious encephalitis are viruses, including Herpes simplex virus type 1 (HSV-1). As the mortality rate of HSV-1 encephalitis could be reduced with early acyclovir treatment, it is imperative to distinguish HSV-1 encephalitis from other type of viral encephalitis as early as possible. However, sophisticated methods for definitive diagnosis of HSV-1 encephalitis are not readily available. We aimed to explore distinctive clinical and laboratory features of HSV-1 encephalitis. All of the adult patients with viral encephalitis hospitalized between 2011-2017 were enrolled, including 16 patients with HSV-1 encephalitis and 51 patients non-HSV-1 viral encephalitis. Determination of viruses in cerebrospinal fluid was performed by PCR tests. Female sex, hyponatremia, and abnormalities in MRI were independently associated with HSV-1 encephalitis (p < 0.05 for each). In particular, hyponatremia (< 135 mEq/L) was found in nine patients with HSV-1 encephalitis (56.3%) and 10 patients with non-HSV-1 viral encephalitis (19.6%) (p = 0.005). As serum sodium is determined easily and quickly in clinical practice, the presence of hyponatremia among patients with viral encephalitis could be helpful for the early diagnosis of HSV-1 encephalitis before cerebrospinal fluid PCR results were available. Moreover, the presence of positive finding in MRI could further support the diagnosis. This is the first study that compared the serum sodium levels among patients between HSV-1 and non-HSV-1 viral encephalitis. We thus propose the diagnostic value of hyponatremia for HSV-1 encephalitis.