This study aimed to investigate the effect of acute mental stress on erythrocyte deformability (ED) in women during different phases of the menstrual cycle and to compare the results with men. For this purpose, healthy males (n = 10) and females (n = 10) (during follicular and luteal phases) underwent Stroop color-word interference and cold pressor tests. Hemoglobin, hematocrit and leukocyte counts before and after this stress test revealed no difference in either group; erythrocyte sedimentation rate was significantly lower in the post-test samples in all. In all groups erythrocyte filtration time was significantly higher and thus ED was significantly lower after the stress test (mean +/- SEM, PRE-TEST: follicular: 3.08 +/- 0.05; luteal: 2.07 +/- 0.05; men: 2.9 +/- 0.05) (POST-TEST: follicular: 4.5 +/- 0.07; luteal: 4.1 +/- 0.07; men: 4.39 +/- 0.1). ED was appreciably influenced by gender and menstrual cycle. Women at the luteal phase had better ED compared to both women at the follicular phase and men, the effect being especially pronounced in the pre-test samples. Our results suggest that stress may induce cardiovascular diseases by lowering ED in both genders. The effect of stress on ED varies with gender and during different phases of the menstrual cycle, which may be explained by variations in the sex hormones.