Background: Sense of coherence (SOC) is defined as a global orientation based on a person's confidence that stimuli are structured and predictable, the resources needed to meet these demands are available, and these demands are seen as challenges, worthy of investment, and engagement. The SOC scale is an instrument measuring how people manage stressful situations and stay well. We aimed to assess the psychometric properties of its Greek version in two samples, people with and without long-term conditions (LTCs). Associations between sense of coherence and mental illness, suicidality, and quality of life were also investigated.