While sex differences in pain reporting are frequently observed, the reasons underlying these differences remain unclear. The present study examined sex differences in self-report and physiological measures of pain threshold and tolerance following the administration of two laboratory pain-induction tasks. The primary study aim centered on determining whether repeated exposure to such tasks would yield sex differences in terms of pain threshold and tolerance. In addition, it was hypothesized that if such differences did exist, negative mood states might account for changes in pain ratings, threshold, and/or tolerance in subsequent exposure to noxious stimuli. Recruited from a convenience sample, 66 participants (44 female and 22 male) were exposed to both thermal and cold noxious stimuli at three separate times, while psychophysiological and self-report data were collected. Because women outnumbered men 2:1, Fisher z transformations were performed to determine whether the observed associations between mood states and pain ratings differed. We found stronger associations between fatigue and thermal-heat pain ratings for men at their first and third exposure to the pain task compared to women (z = 2.11, P < 0.05; z = 3.14, P < 0.001, respectively). Results indicated that women evidenced greater pain tolerance than men on both a behavioral and physiological level; however, they reported greater pain severity than men. Fatigue was also found to be particularly important to reports of pain severity in men and pain tolerance in response to noxious stimuli for women. Possible pathways in which mood states influenced these endpoints are discussed.