Gender specific effects on human eating have been previously reported. Here we investigated sex-based differences in neural activation via whole-brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in response to high energy-dense (high-ED) vs. low-ED visual and auditory food cues in obese men vs. women in both fed and fasted states. The results show that in response to high vs. low ED foods in the fed state, obese men (vs. women) had greater activation in brain areas associated with motor control regions (e.g. supplementary motor areas) whereas women showed greater activation in cognitive-related regions. In the fasted state, obese men had greater activation in a visual-attention region whereas obese women showed greater activation in affective and reward related processing regions (e.g. caudate). Overall the results support our a priori hypothesis that obese women (vs. men) have greater neural activation in regions associated with cognition and emotion-related brain regions. These findings may improve our understanding of sex specific differences among obese individuals in eating behavior.