Fructose consumption has become a normalized part of the standard American diet over the past 40 years. While fructose consumption is a known risk factor of metabolic syndrome, there is increasing evidence that fructose consumption influences brain and behavior. Recently, more interest has been focused on mitochondrial dysfunction as a potential link between metabolic stress and modifications of the central nervous system. Mitochondria are in the unique position of both regulating and being vulnerable to alterations in energy homeostasis. Sex-differences are well categorized in the presentation of metabolic symptoms associated with excessive fructose consumption. Thus, it is important to characterize sex-specific outcomes in the arena of brain and behavior in order to develop better strategies for mitigating the effects of fructose consumption. Therefore, I determined the extent to which a high fructose diet modified physiological outcomes, serum corticosterone, and affective-like behavior in male and female rats. In addition, I examined the potential of excessive fructose consumption to modify synaptic mitochondrial respiration at baseline and following an acute stress experience. In males, serum corticosterone was increased following an acute stress event, and this increase was modified by diet. Fructose consumption resulted in decreased affective-like behavior in the open field test and synaptic mitochondrial respiration was altered by both diet and acute stress experience. In females, fructose consumption altered weight and caloric efficiency. Females demonstrated increased depressive-like behavior in a forced swim test. Corticosterone concentrations were only increased by acute stress experience, and synaptic mitochondrial function was modified by diet in groups that underwent an acute stressor.