We assessed the relationships between burn out, depression and sense of coherence (SOC) using the Maslach Burnout Inventory, Beck's depression inventory and Antonovsky's SOC questionnaire in a large sample of 17 male and 62 female Greek nurses. Analysis showed that SOC in nursing staff was correlated with burnout (BO) and depression, while the latter was correlated to a lesser degree with BO. The relationship of BO with depression seems to be the result of the relationship between depression and SOC. Thus, we could hypothesize that the degree of SOC renders persons either vulnerable or resistant to both depression and BO, though further studies are warranted. In the hospital setting, the intervention by specialized personnel in order to assist nursing staff with BO may be an appealing option. Further, prevention programs aimed at helping individuals prone to BO could also be envisaged.