Objectives Prolonged or excessive stress can have a negative impact on health and well-being, and stress therefore constitutes a major public health issue. A central question is what are the main sources of stress in contemporary societies? This study examines the effects of workrelated and non-work-related stressors and perceived social support on perceived stress within a causal framework. Methods Panel data were drawn from two waves (2013 and 2017) of the population-based health survey "How are you?"conducted in the Central Denmark Region. The analytical sample comprised 9,194 subjects who had responded to both surveys. Work-related and non-workrelated stressors included major life events, chronic stressors, daily hassles and lack of social support. Perceived stress was measured with the 10-item Perceived Stress Scale (PSS). Data were analysed using fixed effects regression in a fully balanced design. Results The largest effects on PSS were seen in own disease, work situation and lack of social support. Other stressors affecting the perceived stress level were financial circumstances, relationship with partner, relationship with family and friends, and disease among close relatives. Most variables had a symmetrical effect on PSS. Conclusions The results point to the need for comprehensive policies to promote mental health that span life domains and include both the individual and the group as well as organizational and societal levels. The study indicates that there are multiple potential entry points for stress prevention and stress management. However, it also shows that disease, work situation and social support weigh heavily in the overall picture. This points to the healthcare system and workplace as key institutional venues for action.