Investigating the molecular mechanisms underlying the decline in cognitive abilities during the ageing process is an important area of research. Peripheral markers of inflammation have recently been implicated in the regulation of neurogenesis (Villeda et al, 2011). We investigated the relationship between circulating cytokines and cognitive abilities in healthy ageing humans. Young (n = 138, mean age ± SD: 23.4 ± 2.7 yrs, 53% female) and old (n = 237, mean age ± SD: 74.4 ± 3.3 yrs, 51% female) participants of the MYOAGE study (McPhee et al, 2013) gave written informed consent. Neurocognitive performance was assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB) and included the Paired Associate Learning (PAL), Spatial Span (SSP) and One Touch Stockings (OTS) tests. Fasted plasma samples were used to assess 31 cytokines using multiplex immunoassays (Millipore). Differences between age groups was analysed via the Mann-Whitney U test. Associations between plasma proteins and cognitive performance were analyzed using the Significance Analysis of Microarray (SAM, v. 4.01 algorithm) software. To visualize age effects, protein data was further transformed into Z-scores and unsupervised cluster analysis was performed using the Gene Cluster (v.3.0) software. The resulting heat map was visualized with Java TreeView (v. 1.1.6). Compared with the young adults, healthy old showed significantly lower performance in episodic memory (PAL = P < 0.0005), working memory (SSP = P < 0.0005) and executive function (OTS = P < 0.0005). Strikingly, sixteen of the cytokines investigated differed significantly between young and old (P < 0.05). Furthermore cluster analysis demonstrated an inflammatory profile of ageing that associated with cognitive differences in both young and old adults. In conclusion, we have characterized the inflammatory profile of healthy ageing and have identified age-related immune markers that associate with cognition.