We tested the extent to which the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with stress response and pain in both men and women. The participants were assessed on measures of perceived pain and state/trait anxiety in association with their COMT allele status. We also measured cortisol and salivary alpha-amylase (sAA) levels since previous research suggests an association between the COMT Val159Met polymorphism, cortisol secretion, and sAA activity. We found significant differences between methionine (Met) allele carriers and valine (Val) homozygotes following a stress manipulation in sAA levels. Met allele carriers had a stronger sAA response when compared to Val homozygotes. Furthermore, Val homozygotes showed a positive correlation between their sAA levels and trait anxiety at baseline and 20 min post-stress manipulation but displayed a negative correlation with the change in sAA levels from baseline to 20 min post-stress manipulation. Finally, state/trait anxiety was significantly correlated in Met allele carriers. These findings add support to the COMT warror/worrier model which states under stressful situations, increased dopamine levels in Val (warrior) homozygotes affords an emotional advantage relative to Met (worrier) allele carriers, who show an increased reactivity to aversive stimuli.