Spirituality has been studied in relation to psychological factors in health for the past decade and has been found to promote positive affect while possibly benefiting health. However, multiple dimensions of spirituality need to be examined systematically before much can be concluded regarding the influence of spirituality on health. One purpose of this study was to test the validity of the four factors of the Psychomatrix Spirituality Inventory (PSI) developed by Wolman using confirmatory factor analysis (CFA): divinity, mindfulness, extrasensory perception, and intellectuality. In addition, the moderation effects of these factors on stress, assessed by cortisol levels, and on perceived cold symptoms induced by a bogus cold viral challenge were investigated among 100 participants as part of a larger study conducted by Nemeroff to identify psychological factors related to perceived cold susceptibility under a bogus viral challenge paradigm. The analysis of CFA among 265 participants indicated that the four-factor Pyscholmatrix Spirituality model did not provide a good fit to the data collected by Nemeroff. The shared variances among factors could be the explanation for failure to confirm these four factors. Women developed more cold symptoms than did men post bogus exposure. Mindfulness and extrasensory perception factors buffered the adverse effects of stress on cold symptoms. A three-way-interaction among gender, stress, and mindfulness indicated that the buffering effects of mindfulness on stress and cold symptoms were stronger for women than for men, and the effects were stronger when the stress levels increased. A three-way-interaction was also found among gender, stress, and extrasensory perception, with the moderation effects of extrasensory perception on stress and cold symptoms stronger for women than for men, and these effects becoming stronger as stress levels elevated. This study is an important step for understanding the relationships among gender, spiritual factors and cortisol levels under laboratory-induced stress. These results have implications for developing preventions or interventions that incorporate mindfulness practices and take extrasensory perception beliefs into consideration for stress reduction and health promotion.