Continuous technical and technological progress, informatization teaching processes, modernization of education and society in general, are placing constant demands on the teaching profession. These trends require from the teachers to have a daily need for improvement and adjustment, which due to its complexity often results in the appearance of stress. Frequent exposure to stressful occurrence can lead to burnout whose consequences are affecting the work efficiency and health of the individual. Studies carried out in developed countries are showing negative relationship between the level of physical activity and the occurrence of work-related stress. Given that recent studies focused on the correlation between the level of physical activity and the high school teachers stress occurrence in the Republic of Croatia are not known, which is specific due to the poor current economic situation, the curricular reform implementation, the post-war period, and the general fact that it is a developing country, this study is representing a scientific but also a practical contribution to the obtained knowledge and a better understanding of the topic. The aim of this study was to determine the level and domain of physical activity (work, transportation, housework, leisure-time) correlation with the occurrence of work-related stress and life satisfaction, and to establish the relative contribution of different domains of physical activity in explaining the work-related stress and life satisfaction of high school teachers. The sample was consisted of 945 high school teachers from the City of Zagreb, stratified according to types of schools and their representation at the level of the City of Zagreb. A sample of seven high schools, twelve vocational schools and two art schools was used. Among the part of questionnaire that describes the sample, the International Physical Activity Questionnaire was used to estimate the level of physical activity (International Physical Activity Questionnaire, IPAQ-LF) (International Consensus Group, Craig i sur., 2003). Work-related stress was estimated with questionnaire Job Affective Well-Being Scale (JAWS) (Van Katwyk, Fox, Spector, & Kelloway, 2000), Physical Symptoms (PSI) (Spector and Jex, 1997) and Teachers Burnout Scale (Seidman and Zager, 1986). Apart mentioned, global life satisfaction was estimated with Satisfaction with Life Scale (SWLS) (Diener i sur.,1985). For statistical data processing, Statistic 12 Windows and IBM SPSS Statistics 26 were used. Negative correlation between general level of physical activity, level of physical leisure-time activity and work-related stress indicators was found using correlation analysis, as well as the positive correlation of physical activity in the housework with the physical symptoms of work-related stress. Positive correlation also was found between the general level and the level of physical activity in the domains of leisure-time, housework and transportation with life-satisfaction. Using hierarchical regression analyzes we determined that the greatest contribution in explaining different indicators of work-related stress, gives the domain of leisure-time, which proved to be a statistically significant positive predictor of multiple criteria variables: total affective work well-being (JAWS), pleasant/positive emotions (JAWS) and physical stress symptoms (PSI). Other predictors showed a statistically significant contribution in relation with: physical activity in the domain of burnout in teaching profession related to administrative support at work, in the transportation domain with pleasant/positive emotions (JAWS), and the domain of housework as a positive predictor of presence of physical stress symptoms (PSI). In explaining life satisfaction, the biggest contribution gives the leisure-time domain, then the transportation domain, while no statistically significant contribution was obtained in the domain of work and housework. Criteria variable of life satisfaction has the highest percentage explained variance (5.2%), based on a set of predictor variables. The scientific contribution of this study is reflected in the obtained knowledge about connection between the level and domains of physical activity (work, transportation, housework and leisure-time) with the work-related stress occurrence, and life satisfaction of high school teachers in the City of Zagreb. Also, it is reflected in the findings about relative contribution of the physical activity levels in different domains: in explaining work stress and life satisfaction of high school teachers, about which no recent studies have been found. The only significant contribution in explaining the various indicators of secondary school teacher’s well-being, actually has only the domain of physical activity in leisure time, while other domains are showing a contribution only for some predictors. The practical contribution is shown in obtained results (even though we cannot claim about the causal link) which are indicating that it makes sense (organizational-, financial-, and personnel-wise) to encourage teachers for physical activity in their free time, in order to increase their personal and work-related wellbeing.