Inflammatory models of neurodegeneration suggest that higher circulating levels of inflammation can lead to cognitive decline. Despite established independent associations between greater body mass, increased inflammation, and cognitive decline, no prior research has explored whether markers of systemic inflammation might mediate the association between body mass and changes in cognitive functioning. To test such a model, we used two longitudinal subsamples (ns=9,066; 12,561) of aging adults from the English Longitudinal Study of Ageing (ELSA) study, which included two cognitive measures components of memory and executive functioning, as well as measurements of body mass and systemic inflammation, assessed via C-reactive protein (CRP). Relatively higher levels of CRP mediated the association of greater body mass and decline in memory and executive functioning over 6 years. Our results suggest that systemic inflammation is one biologically plausible mechanism through which differences in body mass might influence changes in cognitive functioning among aging adults.