Given the well-established impact of COVID-19 on university students’ health and lifestyle parameters, the current study sought to investigate these impacts within an Irish university setting. A cross-sectional design was employed, with a 68-item questionnaire instrument disseminated to all Year 2 undergraduate students in the host institution (N = 2752), yielding a 9.7% response rate (n = 266). This questionnaire elicited students’ self-reported changes to health-related behaviours, mental well-being and academic engagement across 4 defined time-points: (T0: prior to COVID-19, T1: initial onset of COVID-19, T2: during COVID-19, and T3: time of data collection). Many items were adapted from previous Irish research and additional validated scales included the Alcohol Use Disorders Identification Test (AUDIT-C) and the World Health Organisation’s Well-being scale (WHO-5). Key findings revealed that at T1, substantially more males reported ‘good/very good’ general health than females (76.3% vs. 70.8%), while physical activity patterns followed a similar trend at both T0 (80% vs. 66.1%) and T1 (66.7% vs. 61%). A total of 78.4% of participants reported a body mass gain from T0 to T3, thus reflecting the reduced physical activity levels and compromised nutritional patterns across this period. Worryingly, AUDIT-C scale data revealed hazardous drinking habits were evident in both males and females, while fruit and vegetable intake, physical activity levels, and mental well-being among this cohort remained notably sub-optimal. Ratings of positive academic engagement also decreased substantially between T0 (90.3%) and T3 (30.4%). These findings substantiate the rationale for tailored health promotion interventions in university settings to support students’ transition back to traditional programme delivery and, of equal importance, to improve general health and well-being post-COVID-19 within this cohort.