Objective Direct relationships have been found between neuroticism and burnout and between extraversion, conscientiousness, and engagement, key concepts in occupational wellbeing. This study aimed to explore the direct and indirect relationships between neuroticism and exhaustion, the core component of burnout, and between extraversion, conscientiousness, and engagement. Job demands, job resources, and psychological flexibility, a personal resource, were explored as potential mediators. Method Participants completed an online questionnaire at two time points, 1 year apart. Participants were studying nursing, social work, psychology, or occupational therapy at time one (T1) and either studying (n = 18) or working (n = 81) at time two (T2), with no employment information for one participant. At T2 working participants were nurses (n = 36), psychologists (n = 14), occupational therapists (n = 13), social workers (n = 7), other health profession workers (n = 7), and non‐health profession workers (n = 4). At T2 the average age of participants was 31 (standard deviation: 9.52; range: 21–60) and 92% were female. Results The direct relationships between T1 neuroticism and T2 exhaustion, and T1 conscientiousness and T2 engagement were not significant when controlling for the outcome variables at T1, exhaustion and engagement, respectively. Multiple mediation and bootstrapping analyses indicated potential mediation relationships between T1 neuroticism and T2 exhaustion and between T1 extraversion and T2 engagement. Conclusion While personality appears to be important in understanding burnout and engagement, the role of mediation suggests a complex relationship. Further longitudinal and large sample studies are needed to better understand the mechanisms by which personality impacts burnout and engagement.