Abstract Background The present study examined personality, situational and organizational predictors of burnout during COVID-19 in a military setting, based on the salutogenic theory of health (Antonovsky, 1987). Method Questionnaires were completed by 116 reserve Israeli Home Front Command medical staff (71% males). Background variables (e.g., gender), personality variables (self-efficacy and sense of coherence - SOC), situational variables (state-anxiety, self-rated health and sense of threat) and organizational variables (satisfaction with military’s and government’s handling of the COVID-19 crisis) were measured as predictors of burnout. Results Females had higher levels of state anxiety and burnout compared to males. Females also reported a lower level of satisfaction with the military’s handling of the COVID-19 crisis than males. SOC and state anxiety were the only statistically significant predictors of burnout after controlling for sociodemographic variables. The entire model explained 59.4% of the burnout variance. Conclusion In accordance with salutogenic theory, SOC is associated with active adaptation through use of generalized and specific resistance resources to avoid burnout in a stressful milieu. Psychological support, psychoeducation and simulation training are offered to increase manageability in crisis situations. Limitations Following a large dropout rate due to being quarantined, the final sample size was much smaller than planned. Also, although previous longitudinal studies have found SOC to be a causal factor in burnout, the present cross-sectional design limits such conclusions.