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Poor cognition increases risk for negative health outcomes, and this may be explained by associations with systemic inflammation. Previously, amount of repetitive thought (Total RT) interacted with IQ to predict interleukin-6 (IL-6) in older adults. This study continued the investigation of repetitive thought (RT) as an element involved in the effect of cognition on inflammation. Participants (N = 164) came from the Midlife in the United States Refresher project (Mage = 45.33, SD = 11.51, ranges = 25–74; 48.2% female; 85% Caucasian). Cognition was assessed via telephone, inflammatory biomarkers (IL-6, C-reactive protein (CRP), and tumour-necrosis factor-alpha (TNF- α)) analysed after blood draw, and RT derived from daily diary data. Cognition significantly interacted with RT valence (p =.009) to explain CRP after covariate adjustment. Better cognition and more negative RT valence was associated with lower CRP (β = −0.190 [-.387,.008]). Worse cognition and more negative RT valence was associated with higher CRP (β = 0.133 [−.031,.297]). No significant effects were found for IL-6 or TNF-α. RT may interact with cognition to affect different inflammatory biomarkers. Those with worse cognition may benefit more from skills related to regulating thought than those with better cognition. [ABSTRACT FROM AUTHOR]