Salivary antimicrobial protein (AMP) expression is a primary determinant of mucosal immunity. This expression can be altered by exercise. While salivary IgA has been extensively studied, less is known about Lysozyme (Lys) and Lactoferrin (Lac). Knowledge on how sex and menstrual phase affect mucosal immunity is also limited. The purpose of this study was to examine how sex, menstrual phase, and exercise impact IgA, Lys, and Lac expression. Men (n = 9) and women (n = 9) ran for 45 min at 75% VO2(peak). Women were tested in the follicular and luteal phase. Saliva was collected pre-exercise, immediately post-exercise and 1 h postexercise. Pre-exercise, women had higher secretion rates of IgA compared to men (154 +/- 106 vs 85 +/- 44 microg/min) (p < 0.05). Lac secretion rate increased with exercise in both sexes and remained above baseline 1 h after exercise in men (7460 +/- 4839 ng/min), but had returned to pre-exercise levels at 1 h post-exercise in women (5720 +/- 4661 ng/min) (time * sex interaction, p < 0.05). Men had higher secretion rates of Lys (p < 0.05) at each time point compared to women (Men pre-exercise: 31042 +/- 23132, post-exercise: 29521 +/- 13205, 1 h post-exercise: 41229 +/- 31270 ng/min vs Women pre-exercise: 11585 +/- 10367, post-exercise: 22719 +/- 19452, 1 h post-exercise: 17303 +/- 11419 ng/min). Both sexes increased the secretion rate of Lys and Lac with exercise, whereas IgA was unchanged. Menstrual phase did not affect IgA, Lys, or Lac and men and women did not differ in saliva flow rates. In conclusion, regularly menstruating women who are not taking hormonal contraceptives differently express AMPs compared to men.