Bacterial infections of the brain, although uncommon, are extremely severe with high rates of morbidity and mortality. The severity of such infections highlights the importance of protecting the brain from, potentially harmful, external organisms. The trigeminal nerve is the largest cranial nerve with many branches projecting throughout the face and nasal region. These projections merge together and continue into the brainstem (central nervous system). It is responsible for sensations of the face, such as touch and pain, and for motor functions. An infection of Burkholderia pseudomallei causes melioidosis, a disease that is endemic to northern Australia and southeast Asia, and has a high mortality rate (~20% in Australia, ~40% in southeast Asia) even with aggressive antibiotic treatment. As the trigeminal nerve exhibits a direct link from the external environment (nasal cavity) to the brain (central nervous system); it is plausible to hypothesise that this nerve may provide an alternative pathway into the central nervous system. To investigate whether the brain could be invaded via the trigeminal nerve, mice were intranasally inoculated with B. pseudomallei. Within 24 hours of inoculation, B. pseudomallei was found to invade the trigeminal nerve, enter the brainstem (central nervous system), and progressed more than 2,000 μm into the spinal cord. This work highlights a new pathway into the brain for bacteria, which has not been shown before, thus demonstrating that B. pseudomallei can penetrate the brainstem and spinal cord via the trigeminal nerve branches that innervate the nasal cavity.