Background: This study employed a structural equation model to examine the relationships between poor physical health, suicide, depression, psychosocial stress, interpersonal conflict, and panic. Methods: The sample consisted of a large, archived set of mental health treatment-seeking adults who completed a behavioral outcome questionnaire prior to beginning treatment. Results: Results supported the extant literature indicating that poor physical health, depression, psychosocial stress, interpersonal conflict, and panic impose increased risk for suicidal ideation, with depression demonstrating the highest risk for increased suicidal ideation. The results also supported the hypotheses that depression, psychosocial stress, interpersonal conflict, and panic would mediate the association between poor physical health and suicidal ideation. Although no a priori hypotheses were made regarding relationships among the 15 physical illnesses examined, results indicated that HIV/AIDS had the strongest correlation with depression and the weakest correlation with interpersonal conflict. Limitations: Firstly, the study sample was primarily Caucasian, limiting its generalizability. Secondly, causal inferences should be interpreted with caution, due to the quasi-experimental design. Thirdly, these data were self-reported, which create response biases since suicidal ideation is stigmatized. Conclusions: These findings highlight the importance of considering interpersonal factors as potential mediators in the relationship between poor physical health, mental illness, and suicide. Clinically, the impact of an active major depressive episode on an individual who is struggling with a serious physical illness may be strongly predictive of suicidal ideation.