The substantial increase in the number of families facing social exclusion in Europe and its direct relationship with health inequities is a challenge for studies approaching the social determinants of health and policies dealing with welfare and social inclusion. We start from the premise that reducing inequality (SDG10), has a value and contributes on other goals such as improving health and well-being (SDG3), ensuring quality education (SDG4), promoting gender equality (SDG5) and decent work (SDG8). In this study, we identify disruptive risk factors and psychological and social well-being factors that influence self-perceived health in trajectories of social exclusion. The research materials used a checklist of exclusion patterns, life cycles and disruptive risk factors, Goldberg’s General Health Questionnaire (GHQ-12), Ryff’s Psychological Well-being (PWB) Scale and Keyes’ Social Well-being Scale. The sample consists of 210 people (aged between 16 and 64  years): 107 people in a situation of social inclusion and 103 people in a situation of social exclusion. The data treatment involved statistical analysis, including correlation study and multiple regression analysis, aimed at developing a model of psychosocial factors that may act as health modulators, considering social factors as predictors in the regression model. The results showed that individuals in the sample, in a situation of social exclusion, have a greater accumulation of disruptive risk factors, and these are related to having fewer psychosocial and cognitive resources to cope with stressful situations: less self-acceptance, less mastery of the environment, less purpose in life, less level of social integration and social acceptance. Finally, analysis showed that in the absence of social integration and purpose in life, self-perceived health statuses decline. This work allows us to use the model obtained as a basis for confirming that there are dimensions of psychological and social well-being that should be considered stress-buffering factors in trajectories of social exclusion. These findings can help design psychoeducational programs for prevention and intervention with the aim of improving psychological adjustment and health states, as well as to promote proactive and reactive policies to reduce health inequalities.