ABSTRACT: BACKGROUND: Herpes simplex encephalitis (HSE) often leads to severe disability or death. Factors usually associated with outcome include Simplified Acute Physiology Score, age and delay of initiation of acyclovir treatment.Our aim was to determine the impact of Herpes simplex virus (HSV) load in cerebrospinal fluid (CSF) upon HSE outcome. METHODS: We retrospectively determined HSV load in the CSF of 43 patients with confirmed HSE, hospitalized in northern France from 1998 to 2005, using CSF samples collected the day of hospital admission and stored at -20[degree sign]C. We analyzed the association between HSV load and mortality/morbidity by the Glasgow Outcome Scale. Fisher's exact test and Wilcoxon's test were used for statistical analysis. RESULTS: The M/F sex ratio was 1.7 and median patient age was 61 years. Median HSV load in CSF was 2.0 log copies/muL (IQR 25-75=1.2-2.6). The mortality rate was 32.6% six months after HSE diagnosis. Higher age was associated with mortality (p=0.03). Longer delay in acyclovir initiation tended to be associated with higher mortality but did not reach statistical significance (p=0.08). Severe disability and death due to HSV were associated with a higher Knaus score (p=0.004), later acyclovir initiation (p=0.006), older age (p=0.04) and presence of red blood cells in CSF (p=0.005). HSV load in CSF was neither associated with mortality (p=1.00) nor with morbidity (p=0.90). CONCLUSION: In this study, HSV load in CSF was not found to be associated with poor outcome in patients with HSE. These data do not support measurement of HSV load at admission in patients with HSE.