Introduction: The aim of the study was to examine basal hypothalamic-pituitary-adrenal (HPA) axis activity and to determine associations of various covariates (gender, sleep-wake rhythm, demographic, academic, life style and health-related characteristics) with altered daily salivary cortisol profiles in late adolescence. Materials and methods: The total analytic sample consisted of 903 Croatian secondary school students aged 18 - 21 years (median 19 years). Salivary cortisol was sampled at home at three time points over the course of one week and its concentrations were measured by using the enzyme immunoassay. Results: In comparison to males, female students had a higher cortisol awakening response (CAR) (median 4.69, IQR 10.46 and median 3.03, IQR 8.94, respectively; P < 0.001), a steeper (“healthier”) diurnal cortisol slope (DCS) (median 0.51, IQR 0.55 and median 0.44, IQR 0.51, respectively; P = 0.001), and a greater area under curve with respect to ground (AUCG) (median 206.79, IQR 111.78 and median 191.46, IQR 104.18, respectively; P < 0.001). Those students who woke-up earlier and were awake longer, had a higher CAR (P < 0.001), a flatter (“less healthy”) DCS (P < 0.001), and a greater AUCG (P < 0.001), than students who woke-up later and were awake shorter. Less consistent but still significant predictors of salivary cortisol indexes were age, school behaviour, friendship, diet healthiness and drug abuse. Conclusion: Gender and sleep-wake up rhythm were major determinants of the altered daily salivary cortisol profiles in late adolescence. The predictive power of other covariates, although less clear, has a potential for identifying vulnerable subgroups such as male drug users and females without a best friend.