Purpose: Acute bacterial meningitis (ABM) is a severe disease with an overall poor outcome. Neurofilament (NFL) has shown to be a promising biomarker of neuroaxonal injury in various neurological disorders but has not been investigated in ABM. The aims of this study were (i) to obtain a temporal profile of NFL, neuron-specific enolase (NSE) and S100B in serum during ABM, and (ii) to evaluate their use as biomarkers of severity (Glasgow coma score) and prognosis (Glasgow Outcome Score, GOS and death) in severe ABM. Methods: Fifteen adults with severe community-acquired ABM who were admitted to the intensive care unit (ICU) and fulfilled the inclusion criteria were included. Lumbar puncture and blood tests were performed on admission, and blood tests were performed three times daily during the ICU stay. GOS was obtained day 30. Results: Serum NFL was significantly elevated in ABM patients compared to healthy controls, both at admission and throughout the observation period (p <.01). NFL increased significantly from day 1 up to day 3–6 (p <.0001), peaking day 6. NSE increased significantly from admission up to day 3 (p <.01). At day 5–6, the serum values were not significantly different from values at admission. The highest median serum value of S100B was observed at admission (0.10 µg/L, IQR 0.06–0.14), significantly decreasing day 4–6 (p <.05). None of the investigated biomarkers revealed significant correlation with severity and prognosis. Conclusion: This study represents a first clinical observation of the temporal profile of NFL in serum, in severe ABM. No correlation with severity or prognosis.