BACKGROUND : Increased investment in optimal student mental health and well-being has been noted by universities around the world. Studies show the need for contextually relevant, granular understandings of specific aspects of student mental health and well-being. METHODS : A survey was conducted at two time points – at the beginning and end of the academic year – at a large, urban university in South Africa. The Mental Health Continuum-Short Form, the Flourishing Scale, and the Fragility of Happiness Scale were used in the testing of undergraduate students from a variety of scientific disciplines. Two separate comparisons were made, based on the baseline data (n = 551) and the follow-up data (n = 281). In Comparison 1 (baseline, n = 443; follow-up, n = 173), two independent, biographically (very) similar groups were compared. Comparison 2 (n = 108) compared the results from the baseline and follow-up of the same group of students who completed the instruments at both time points. RESULTS : Results indicate a significant decline in mental health and well-being for both groups (independent and dependent) over the course of the academic year. Both follow-up groups were found to have lower psychological, emotional and social well-being, psychological flourishing, and reduced mental health, in comparison with the baseline groups. CONCLUSIONS : The statistically significant decreases in the mental health and well-being of participants in this study indicate the need for substantive interventions to support student mental health and well-being. Strong foci for well-being interventions should include self-efficacy, sense of direction, meaning and creating a sense of belonging.