The level of secretory immunoglobulin A (sIgA) measured in saliva is downregulated during periods of chronic stress. In contrast, the response to an acute stress challenge is a transient increase. The process of awakening is associated with stress neuroendocrine activation characterised by increases in salivary cortisol. We therefore examined if this period of hypothalamic-pituitary-adrenal (HPA) activation was associated with changes in salivary sIgA. Associations of sIgA with the diurnal cortisol cycle were also investigated in a separate study. The awakening cortisol response was measured in 30 healthy day-active young adults. There was a marked elevation from the first awakening level over the succeeding 30 min. SIgA showed the opposite response with a marked fall from the highest first awakening concentration in the same samples over the same period. The cortisol rise was significantly correlated with the sIgA fall (r = 0.42). Salivary sIgA showed a similar diurnal cycle to cortisol in a study on eight healthy young adults. An early morning acrophase was followed by a decline to a stable base some 6 h after awakening. The physiological significance of these relationships and possible implications for vulnerability to infection are discussed.