John Cunningham virus (JCV), a member of polyomaviridae family, has been described as a cause of the progressive multifocal leukoencephalopathy (PML). It is a potentially fatal, disabling demyelinating infection of the brain occurring mostly in the setting of immunosuppression. A few cases of JCV-associated meningitis and encephalitis have been described in literature. We report a case presenting with laboured breathing and reduced conscious level, who after thorough investigations was diagnosed to be a case of PML.