BackgroundPrevious studies conducted in various nationally representative samples of the general population show that positive mental health is related to social prosperity. However, specific studies in university populations are scarce. In this study, we set out to explore factors associated with mental well-being (MWB) in a representative sample of first-year university students in Spain. MethodsMWB was assessed with the short version of the Warwick-Edinburgh Mental Well-Being Scale. Multinomial logistic regressions were performed to explore the association between different blocks of factors, including relational, adversity, stress, lifestyle, spiritual, health, and self-perceived health variables with high and low MWB, controlling for sociodemographic and university-related variables. ResultsData from 2082 students (18.6 ± 1.2 years; 56.6 % females) were analysed. Being male, being born in a foreign country, “high” self-perceived support, and “high” self-perceived mental health increased the odds of high MWB. Growing up in the suburbs, stressful experiences, and anxiety disorders reduced the odds of high MWB. Mood and anxiety disorders increased the odds of low MWB. “Middle” self-perceived support, sleeping ≥8 h per day, and “high” self-perceived mental health reduced the odds of low MWB. LimitationsThe cross-sectional design precludes establishing causal relationships. Data were collected in the 2014–15 academic year using self-reported online surveys. ConclusionThe factors associated with high and low MWB do not always mirror each other, so specific plans are needed to successfully address each of the two poles. Interventions and policies targeting these factors for health promotion and disease prevention would improve the MWB of university students.