Purpose: To determine if prolonged sitting negatively impacts cognitive function, cerebral perfusion, and central cardiovascular hemodynamics; and secondly, to test whether weight or physical activity status alters this response. Methods: Participants (N=20, age=26±7; BMI=30±7 kg/m2; 7 female) were taken through 3 hrs of sitting followed by a 10-min walk (treadmill). Cognitive function was assessed during sitting (10, 60, 120, and 180 mins) and following the walk using a color/word Stroop test. Cerebral perfusion was measured via near infrared spectroscopy (total hemoglobin— tHb). Central cardiovascular hemodynamics and aortic stiffness (pulse wave velocity— PWV) were measured using the SphygmoCor XCEL device before, during and after sitting. Body mass index, %-bodyfat, and accelerometry data were used to characterize weight and physical activity status. Results: Following sitting, there was no change in Stroop completion time; however, both Color and Text times significantly decreased following the walk (e.g., Color Time: 10 mins sitting, 19±3 sec vs. Post walk, 16.7±3.6 sec, p<0.001). A similar finding was noted for change in reaction time (p=0.036). Cerebral perfusion did not change during sitting, but increased during the walk (180 mins sitting=415±38 $μ$M vs. 10 min walk=432±42 $μ$M; p<0.001). There was a significant increase in PWV for normal weight (Pre-sit=5.7±1 vs. Post-sit=6.1±1.1 m/s, p=0.009), but not in participants classified obese (p=0.02). Conclusion: These findings suggest that prolonged sitting does not alter cognitive function or cerebral perfusion, but sitting does increase aortic stiffness in normal weight individuals. Walking can improve cognitive function, an effect possibly related to increases in cerebral perfusion.