Introduction: Free-living amoeba is ubiquitous in fresh water, mud, and moist soil; although seldom pathogenic to humans, Naegleria fowleri, Acanthamoeba spp., and Balamuthia spp. are known to cause infections of the central nervous system. Methods: We report two interesting cases, both of which presented with a rapid-onset and fulminant course. The first case details a 36-year-old male with a history of surgically corrected nasal bone fracture 15 years back, who presented with acute onset of fever, headache and convulsions. Results: Direct smears of cerebrospinal fluid (CSF) revealed motile trophozoites resembling N. fowleri and were later confirmed by molecular diagnosis (polymerase chain reaction [PCR]). Subsequently, the source was identified as water used for religious purposes. Unfortunately, the patient succumbed to cardiac arrest. The second case is that of a 4-year-old boy from Palakkad district, Kerala, who presented with sudden onset of nasal discharge, fever, headache, vomiting, seizures and altered sensorium. His CSF smear examination showed motile trophozoites resembling Acanthamoeba spp. While undergoing treatment, he seized thrice before going into cardiac arrest. Despite extensive resuscitation measures, the child could not be revived and passed away. The postmortem CSF sample sent for molecular analysis confirmed infection by Acanthamoeba spp. Conclusion: Rapid progression and lack of definite treatment options make this a highly fatal condition. Although clinical presentations of both patients were indicative of pyogenic meningitis, parasitic infection was suspected when the CSF was found turbid with no bacteria, high protein, and low sugar. High index of suspicion helped us to get an early preliminary diagnosis from direct microscopy. © 2024 Elsevier B.V., All rights reserved.