Globally, university students face substantial psychological pressures, and stress-related mental health disorders are recognized as major public health concerns. While biomarkers such as cortisol have been extensively studied, integrated analyses of neuroendocrine-immune-circadian interactions remain limited. In this cross-sectional study with two complementary components, psychometric assessments of 637 undergraduates revealed that 90.4% experienced moderate-to-high perceived stress. These stress levels correlated with fatigue (r = 0.41, p < 0.01) and poor sleep quality (r = 0.35, p < 0.01). A second component involved laboratory-based diurnal biomarker profiling of 33 high-stress and low-stress participants, revealing stress-dependent physiological patterns. Specifically, high stress was associated with sympathetic activation (α-amylase↑), HPA axis dysregulation (altered diurnal cortisol patterns), circadian disruption (melatonin↑), and mucosal immune activation (IgA ↑ , lysozyme↑). The coupling of α-amylase and lysozyme suggested neuro-immune coordination (r = 0.52, p < 0.001). These findings indicate that salivary biomarker profiles are associated with perceived stress. Sleep quality and fatigue warrant further investigation as potential intervention targets in future longitudinal studies.
