One of the goals of research in various psychological approaches is the recognition of factors having a role in individuals’ vulnerability. Investigating and identifying psychological and physical vulnerability factors presents a new direction in the prevention, diagnosis and adopted treatment methods. Individuals might have psychological and physical vulnerabilities that predispose them to mental and physical disorders. One of the social traumatic variables is social isolation. The purpose of the present study was to predict psychological and physical vulnerabilities according to social isolation. The moderating role of gender and marital status on the relationships between social isolation and psychological/ physical vulnerability was also investigated. A total of 419 individuals (206 men, 193 women) from the general population of Tehran answered to Symptom Checklist (SCL-25) and Social Loneliness Scale (SLS). The results showed positive correlations between social isolation with psychological and physical vulnerabilities (P < 0.01). Hierarchical regression analysis revealed that gender and marital status could not moderate the relationship between social isolation and physical vulnerability as well as psychological vulnerability. According to the results of the present study, it can be concluded that early identifying social isolation can be served at a preventive level. Social isolation also can be managed and treated within the models of interventions.