Objectives: Psychological distress among people with physical disabilities (PWPD) might affect their physical morbidity, reduce their quality and duration of life, and increase their need for health care services. Therefore, it is essential to explore the factors that might affect psychological distress among PWPD. The current study assesses the association between demographic factors (gender, education, and employment status), health- and disability-related factors (type of disability, visibility of the disability, disability duration, and self-rated health), and psychosocial factors (perceived discrimination and perceived social support), and psychological distress among PWPD in Israel. Design: The data were collected through structured questionnaires administered to a sample of 433 PWPD. Results: The findings suggest negative associations between education, employment status, duration of disability, self-rated health, and perceived social support, and psychological distress among PWPD. In addition, the findings indicate a positive association between perceived discrimination and psychological distress. No association was found between gender, type of disability, and visibility of the disability, and psychological distress. Conclusions and implications: PWPD who are unemployed, less educated, with a shorter duration of disability and lower self-rated health, as well as those who feel more discriminated against and less social support, are more likely to experience higher levels of psychological distress. Therefore, it is important to raise PWPD’s awareness of their rights and of the social possibilities and services available to them, to provide them with mental help, to engage in extensive social activities aimed at providing resources to PWPD, and to act to eliminate discrimination.