Background: On 4 August 2020, an explosion shook Beirut, killing more than 200 people and leaving thousands injured or homeless. Aims: This study examined mental health of university students through a cross-sectional online survey between December 2020 and January 2021. Methods: The questionnaire consisted of the WHO-5, sense of coherence (SoC), future anxiety, self-developed subjective symptoms of mental strain (SSMS), and items assessing proximity to explosion, extent of injury and house damage. Gender, study level and social status were used as sociodemographic characteristics. Results: Of 1042 participants, 30.8% were at 0–7 km from explosion; 38.1% reported physical injuries; and 12.4% saw their home damaged. Two third (60.3%) reported ≥3 SSMS, and 73.4% reported low well-being. Students with low well-being were more often female and master students (p < 0.001). Females were more often affected by ≥3 SSMS (p < 0.001). Regression analysis with low well-being as dependent variable revealed significant associations with study level (OR: 2.30–2.94), future anxiety (OR: 2.72–4.34) and SoC (OR: 1.81–5.61). For ≥3 SSMS, females (OR: 3.09), moderate/very close distance (OR: 2.13–4.98), injury/death of family member or friend (OR: 2.07–2.06), house damage (OR: 1.72) future anxiety (OR: 1.97–3.11) and SoC (1.79–2.88) were significant predictors. Discussion: Preventive mental health strategies that strengthen SoC and outlook on future could protect against SSMS and low well-being following major trauma.