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Overweight and obesity are well-known independent risk factors for stroke in the general population although uncertain in the case of the elderly, according to the obesity paradox. Little is known about underlying mechanisms. Our study aims to assess whether there is a relationship between excess body weight (measured as waist circumference) and poor cerebral hemodynamics (measured by transcranial Doppler parameters: basal, mean flow velocity (MFV), and dynamic, cerebrovascular reserve (CvR) in the right middle cerebral artery (RMCA)). A possible underlying molecular mechanism was analyzed via plasma leptin, adiponectin, TNF-α, IL-6, VCAM, and CRP levels. One hundred sixty-five subjects were included. Bivariate and multivariate regression showed a linear correlation between waist circumference and hemodynamics in RMCA, with clear gender effects: MFV (global NS, men β - 0.26 p < 0.01; women NS), CvR (global: β - 0.15 p < 0.01; men: β - 0.29 p < 0.01, women: β - 0.19 p < 0.09). For subjects above 65 years, there is no significant relationship between AbP and cerebral hemodynamics. In multivariate regression models, only leptin correlated independently with MFV in RMCA (β 7.24, p < 0.01) and CvR (β - 0.30, p < 0.01). In both cases, waist circumference remains significantly related to both parameters. There is an inverse linear correlation between excess body weight and cerebral hemodynamics, independent of other vascular risk factors and clearly influenced by gender. This relation disappears in the elderly population. Leptin might play a role in this relationship. Nevertheless, there must be another associated mechanism, not identified in this study.