College student’s mental health (MH) is an important issue for their development and academic success. Enrolment in higher education set up a multiple transition that cause stress, imbalance and a challenging adjustment, with major impact on a personal, and academic level. In Portugal, little is known about the relationship between biopsychosocial variables and mental health of college student’s. This study aims to: 1) describe the mental health college students in terms of psychological well-being and distress; 2) explore the relationship between college student’s mental health, well-being and psychological distress and: sociodemographic, relational, academic characteristics; health behaviours; social support perception (SSP); satisfaction with academic life (SAL); negative life events (NLE); psychological vulnerability (PV) and vulnerability perception (VP) 3) To identify predictors of well-being and psychological distress in CE. Using a cross-sectional correlational trial and a non probabilistic sample of 560 under graduating students attending the 1st and 2nd year, in 2014/15 during the 1st semester, Lisbon District, data was collected from an online self-report inquiry form "Metal Health Survey for College Students" was used, containing variables and measures: sociodemographic, relational; academic; health behaviours; Mental Health Inventory (MHI); Social Support Satisfaction Scale (SSSS); Negative Life Events Inventory (NLEI); Life Academic Satisfaction Scale (LASS); Psychological Vulnerability Scale (PVS) and Perception of Vulnerability (PV). Throughout the course of research formal and ethical aspects were observed. Quantitative techniques, descriptive and inferential statistical analysis was performed. Results reveal a good mental health (M = 158.87, SD = 29.49), but 16.6% are in the MH-Low level, and 10% have self-harmful behaviours. SSSS is high, and generally students are satisfied with academic life, most had no negative life events, and they have moderate psychological vulnerability, but they don’t feel vulnerable. We found that MH is positively correlated with: high socioeconomic level; have an affective stable and satisfactory relationship; have good academic performance; sleep 7 or more hours; do not drugs, be satisfied with social support and academic life, never had negative life events, having less psychological vulnerability and have a lower perception of vulnerability. Also, MH- High level is correlated with: SE-Low/Medium; conflictual/tense or short relationship; insufficient academic performance; sleep less than six hours; take drugs; having self-harm behaviour; psychological vulnerability and feel If vulnerable. Regression analyses indicate that males; have a close relationship/dating satisfactory, good academic performance, exercising, sleeping 7 hours, satisfaction with social support and academic life are very significant positive predictors of psychological well-being. Conversely females, low socioeconomic level, aged 21-24 years, sleeping less than 6 hours, having moderate psychological vulnerability and perception of vulnerability are strong negative predictors of psychological distress. We identified several biopsychosocial predictors of well-being and psychological distress in college student’s. These data should be considered to design specific programs, based in metal health promotion and prevention of morbidity, to decrease MH deficits and problems of mental health.