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Background Central Nervous System (CNS) infections frequently result in devastating consequences although the aetiology is seldom definitively identified. To address this knowledge gap, we conducted a prospective study to describe the epidemiology of CNS infections in Singapore. Methods Patient enrollment was conducted in 5 adult tertiary hospitals in Singapore, between August 2013 and December 2016. Patients aged ≥16 years who met the inclusion criteria were enrolled. Demographic data, neuroimaging, neurophysiology and biochemical results were collected. Cases were classified as “Confirmed” or “Probable” depending on whether the aetiological agent was detected by either culture or molecular methods in the CSF. The modified Rankin Scale (mRS) was recorded at enrollment, 2 weeks and 6 months, with scores of 0–2 classified as good and 3–6 as poor outcome. Results A total of 2061 patients were screened, of whom 199 met the inclusion criteria. A total of 106 (53.2%), 65 (32.7%) and 28 (14%) cases of meningitis, meningoencephalitis and encephalitis were diagnosed, respectively. An aetiologic agent was identified in 119 (60%) of cases. Mycobacterium tuberculosis (MTb) was the most common cause of meningitis and meningoencephalitis with 23 (13.5%) cases. Herpes simplex virus was the most common aetiology for encephalitis with 3 (10.7%) cases. Immune-mediated aetiologies accounted for 8 (4%) of the total cases. Fatal outcomes were observed in 7 (3.5%) patients. The absence of focal weakness (aOR 0.024 95% CI 0.001–0.535 P = 0.018) and absence of altered mental status (aOR 0.03; 95% CI 0.002–0.43; P = 0.009) at admission predicted good outcomes at 6 months. Vomiting was associated with poor prognosis (aOR 17.91; 95% CI 1.12–286.04; P = 0.041). Conclusion It is surprising that MTb was the most common aetiologic agent although none were fatal. Our study identified aetiologic diagnoses, clinical and biochemical results that correlated with outcome of CNS infections although it also underscores the need for better diagnostic tools for aetiologic confirmation. Disclosures All authors: No reported disclosures.