Background/Aims: Glutamate is the primary excitatory neurotransmitter in the central nervous system, and elevated levels have been implicated in neurotoxicity. Corneal nerves are integral to ocular surface health and abnormalities can contribute to dry eye disease (DED). This study evaluates the relationship between serum glutamate levels, DED signs and symptoms, and corneal nerve parameters. Methods: A total of 124 veterans evaluated at the Miami Veterans Affairs Eye Clinic were included. Participants completed standardized questionnaires assessing ocular surface symptoms and pain, underwent comprehensive ocular surface examination and in vivo confocal microscopy, and provided blood samples for serum glutamate analysis. Results: Mean age was 55.67 ± 4.59 years; 90.3% were male, 55.6% White, and 35.5% Hispanic. Serum glutamate ranged from 0.26 to 3.16 µM/µL (mean 1.22 ± 0.57 µM/µL). Glutamate levels were not associated with DED symptoms as assessed by standardized questionnaires. Higher glutamate levels were linked with DED signs including reduced tear production (right eye: r = −0.05, p = 0.55; left eye: r = −0.25, p = 0.01) and increased corneal staining (right eye: r = 0.10, p = 0.29; left eye: r = 0.20, p = 0.03). Most notable were associations between elevated glutamate and corneal nerve health, including reduced corneal sensation (right eye: r = −0.20, p = 0.03; left eye: r = −0.18, p = 0.047) and decreased corneal nerve fiber width (r = −0.23, p = 0.01). Conclusions: Our findings support an association between systemic neurochemical status, specifically circulating glutamate, and ocular surface and corneal nerve health.