BACKGROUND: Sexual dimorphism in the hypothalamic pituitary adrenal (HPA) axis can influence sex-specific patterns of response to stressors. While a host of findings exist on sex differences in stress-induced activity of the HPA axis and associated mechanisms in rodents, less is known about the intricacies of sex differences in stress responsivity in humans. Accordingly, the overall aim of the present study was to investigate psychological variables that may account for differences in the cortisol stress response between men and women. METHODS: Eighty-six participants filled out self-report measures of anxiety (STA-Y), aggression (BPAQ), and happiness (SHS). We then exposed all participants to a one-minute Cold Pressor Test (CPT) that was maintained between 3-5° C. Cortisol and pain ratings were assessed. We focused on the 20-minute time point for cortisol since that is when cortisol is near its peak post-stress. RESULTS: Women reported higher pain ratings compared to men. Women also showed a positive relationship between pain ratings and cortisol. Aggression was significantly related to cortisol levels in men, but not in women. Similarly, trait anxiety was positively related to cortisol levels in men, but not in women. Happiness was unrelated to cortisol levels in women and men. Follow-up regressions were conducted separately for men and women. A significant model was found for cortisol in men only with trait anxiety, aggression, and the interaction between trait anxiety and aggression. CONCLUSIONS: The current study builds on previous reports by showing that aggression and anxiety differentially influence the cortisol response to an acute stress in men and women.