Inflammation (immune system activation) affects neuronal function and may have consequences for the efficiency and speed of functional brain processes. Indeed, unusually slow psychomotor speed, a measure predictive of behavioural performance and health outcomes, is found with obesity and ageing, two conditions also associated with chronic inflammation. Yet whether inflammation is the mediating factor remains unclear. Here, we assessed inflammation by indexing interleukin-6 level in blood and measured psychomotor speed as well as indices of selective visual attention in young (mean = 26 years) or old (mean = 71 years) adults (N = 83) who were either lean or currently significantly overweight (mean body mass index = 22.4 and 33.8, respectively). Inflammation was positively and significantly correlated with psychomotor speed, age, and body mass index but not with attention measures. Using mediation analyses we show for the first time that inflammation fully accounts for the significant psychomotor slowing found in those with high BMI. Moreover, we further show that age-related psychomotor slowing is partially mediated by inflammation. These findings support the proposal that reducing inflammation may mitigate weight- and age-related cognitive decline and thereby improve performance on daily tasks and health outcomes more generally.