Background: The COVID-19 pandemic has profoundly impacted global mental health, exacerbating anxiety, depression, and insomnia, with prevalence rates of 25–30%, 27–32%, and 30–45%, respectively—2–3 times higher than pre-pandemic levels. Neuroticism, a key personality trait from the Big Five model, characterized by heightened negative emotions and stress reactivity, has been linked to increased vulnerability. Meta-analyses show neuroticism triples anxiety risk (OR=3.21; 95% CI: 2.35–4.39) and correlates strongly with insomnia (r=0.46, p<0.001) and depression during the pandemic. In Mongolia, empirical data on neuroticism's role remains limited. Objective: This study examines whether neuroticism acts as a risk factor for anxiety, depression, and insomnia among hospitalized patients during COVID-19. Methods: A cross-sectional descriptive study enrolled 552 patients (72.3% COVID-19 cases, 27.7% controls) from tertiary hospitals in Mongolia (2024). Participants (mean age 52.8±15.5 years; 60.5% female) completed self-reported questionnaires: Eysenck Personality Inventory (EPI) for neuroticism, PHQ-9 for depression, GAD 7 for anxiety, ISI for insomnia, and PCL 5 for PTSD. Sociodemographics were assessed. Data were analyzed using SPSS 26.0 with chi-square tests (p<0.05 significance). Instruments showed high reliability (Cronbach’s α=0.81–0.89). Ethical approval was obtained from MNUMS Ethics Committee (No. 2024-Psy-17). Results: Overall, 79.5% were depression free, 84.8% anxiety-free, and 77.5% insomnia-free. High neuroticism (n=381) was significantly associated with depression (24.4% vs. 11.7%, p<0.001), anxiety (18.6% vs. 7.6%, p<0.001), insomnia (28.3% vs. 9.4%, p<0.001), and any mental disorder (21.3% vs. 7%, p<0.001), but not PTSD (p=0.472). Cholerics (n=200) showed elevated risks (depression 29.5%, insomnia 34.5%, p<0.001), while sanguines/phlegmatics were protective. Verbal expression and trust levels showed no significant associations. Conclusion Neuroticism significantly heightens risks for anxiety, depression, and insomnia during COVID-19, underscoring the need for targeted psychological interventions. Temperament-informed screening could enhance prevention strategies in crisis settings.