Sleep disturbance has been found to trigger a stress response with a subsequent activation of the psychoneuroimmunological (PNI) pathway associated with adverse health outcomes. This study aimed to assess the association among selected PNI biomarkers, sleep disturbances, and adverse health outcomes (depressive symptoms, physical symptoms). A stratified, quota sample (14 poor sleepers and 15 good sleepers) was drawn from a pool of healthy college women from a larger scale of study. The participants reported their sleep, stress, depressive, and physical symptoms. Wrist actigraphy was used to collect objective sleep data, and the Enzyme-Linked ImmunoSorbent Assay was used to assess PNI biomarkers. Poor sleep quality, higher stress perception, elevated serum serotonin, and lower serum interleukin-10 explained 75.3% of the variances for the depressive symptoms. Poor sleep quality along with delayed peak activity rhythms accounted 31.4% of the physical symptoms. High serotonin and tumor necrosis factor-α were the significant predictors for poor sleep efficiency, and serotonin was the single significant predictor for poor daytime functioning. Stress and sleep disturbances negatively impact the health of college women and should be as part of regular check-ups on campus. PNI effects on health outcomes should be further explored. Educational materials in the areas of sleep hygiene, health impacts from sleep disturbances, and strategies to maintain synchronized circadian rhythms should be mandatorily included in the college curriculum