The workplace is not immune to conflict and stress, specifically when fulfilling people's responsibilities at great personal costs. Doctors and nurses are always on the frontline in hospitals, vaulting from one stressful high-stakes situation to the next. The HEXACO model of personality traits: Honesty-humility, Emotionality, Extraversion, Agreeableness, Conscientiousness, and Openness, has long been hypothesized to be a major predicting factor when determining individuals' responses to stress and susceptibility to experiencing depression. Most research suggests that personality traits resonate with a person's cognitive abilities and how they can deal with stress and depression. However, there is a lack of research on their correlation to depression severity in the Middle East. The current study aimed to investigate the impact of HEXACO personality traits and socio-demographic factors on depression amongst doctors and nurses. A sample of 170 doctors and nurses (62.1% doctors) completed HEXACO-60 and PHQ-9 depression severity questionnaires. The data were analyzed through descriptive statistics, independent samples t-test, ANOVA, correlation, and regression analysis. The findings showed that Honesty-humility was the strongest predictor, while extraversion was the second strongest. Emotionality had the least impact on depression. The relationship between Agreeableness and Openness to Experience with depression was insignificant. However, gender, age, working hours, and work experience were significant predictors of depression. Marital status and level of specialization were insignificant predictors. Thus, it was concluded that not all HEXACO traits and socio-demographics predict depression. Study findings could be utilized in the implementation of employee recruitment, job crafting, positive psychology, and coaching.