Background: The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort.Methods: Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-α) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified.Results: The average age of participants was 53 years (SD = 20, interquartile range = 38). Both α-carotene (P = 0.01) and β-carotene (P < 0.001) correlated positively with plasma total antioxidant capacity. A positive correlation was observed between α-carotene and CSF TNF-α levels (P = 0.02). β-cryptoxanthin (P = 0.04) and lycopene (P = 0.02) inversely correlated with CSF and plasma IL-6 respectively. A positive correlation was also observed between lycopene and both plasma (P < 0.001) and CSF (P < 0.01) [NAD(H)]. Surprisingly no statistically significant associations were found between the most abundant carotenoids, lutein and zeaxanthin and either plasma or CSF markers of oxidative stress.Conclusion: Together these findings suggest that consumption of carotenoids may modulate inflammation and enhance antioxidant defences within both the central nervous system (CNS) and systemic circulation. Increased levels of lycopene also appear to moderate decline in the essential pyridine nucleotide [NAD(H)] in both the plasma and the CSF.