Perception of stress with consequent activation of a neuroendocrine cascade causes changes in immune function that may be bi-directional, with alterations in basal levels of biological parameters outside the optimal range. In this cross-sectional study of 302 healthy persons (males 56.3%, females 43.7%) aged 41-46 years, higher stress levels, as assessed by questionnaire measures of recurrent and recent perceived stress, were associated with a 4-fold greater risk of having a high compared to mid-range serum neopterin concentration, indicating activation of cellular immune mechanisms [adjusted odds ratio, OR; (95% confidence intervals, CI): Low stress=1.00 (reference group); Medium stress=4.13 (1.51, 11.29); High stress=4.63, (1.35, 15.83), p for trend=0.01]. Higher stress levels were associated with a 3-fold greater risk of having signs of humoral immune activation, as indicated by salivary IgA concentration [high compared to mid-range salivary IgA: Low stress=1.00 (reference group); Medium stress=1.06 (0.48, 2.34); High stress=3.62 (1.26, 10.39), p for trend=0.02], but also a 4-fold greater risk of humoral immune depression [low compared to mid-range IgA: Low stress=1.00 (reference group); Medium stress=1.72 (0.74, 3.99); High stress=4.38 (1.47, 13.00), p for trend=0.02]. In conclusion, in this cross-sectional study, higher stress levels were associated with higher serum neopterin and both elevated and depressed salivary IgA levels. These findings emphasise the importance of considering that stress may have bi-directional effects on immune mechanisms, and are consistent with an activational effect of chronic, perceived stress on cellular immunity, and a bi-directional effect on IgA levels, one aspect of humoral immunity.