Acute prolonged sitting leads to cerebrovascular disruptions. However, it is unclear how prolonged sitting interacts with other common behaviors, including high- (HGI) and low- glycemic index (LGI) meals. Using a double- blind randomized cross- over design, this study evaluated the effects of prolonged (3 hr) sitting, with a high- (HGI; GI: 100) or low- glycemic index (LGI; GI: 19) meal on total brain blood flow (QBrain) and executive function. Eighteen young, healthy, active participants (22.6 [3.1] y, 33% F, 24.3 [3.7] kg/m2) sat for 3 hr after consuming an HGI or LGI meal. Using Doppler ultrasound to measure internal carotid (ICA) and vertebral (VA) artery blood flow, QBrain was calculated: (ICA blood flow + VA blood flow) × 2. Executive function was assessed using the Stroop Test and Trail Making Test— Part B. Brain fog was measured using a modified Borg Category Scale with Ratio properties (CR10). Following 3 hr of sitting, there was a significant decrease in QBrain with time (p = .001, ES = −0.26), though there were nonsignificant interaction (p = .216) and condition effects (p = .174). Brain fog increased (p = .024, ES = 0.27) and Stroop re- action time worsened with time (p = .001, ES: −0.40), though there were nonsignifi- cant condition effects for brain fog (p = .612) and the Stroop test (p = .445). There was a nonsignificant condition effect (p = .729) for the Trail Making Test— Part B, but completion time improved with time (p = .001, ES = −0.40). In conclusion, 3 hr of prolonged sitting decreases QBrain and executive function independent of glycemic index in young, healthy adults.