AbstractAcute exercise suppresses appetite and alters food‐cue reactivity, but the extent exercise‐induced changes in cerebral blood flow (CBF) influences the blood‐oxygen‐level‐dependent (BOLD) signal during appetite‐related paradigms is not known. This study examined the impact of acute running on visual food‐cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five‐minute pseudo‐continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD‐fMRI was acquired during a food‐cue reactivity task before and 28 min after exercise/rest. Food‐cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trialp≤ .018). No time‐by‐trial interactions for CBF were identified (p≥ .087). Exercise induced moderate‐to‐large reductions in subjective appetite ratings (Cohen'sd= 0.53–0.84;p≤ .024) and increased food‐cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise‐induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food‐cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.