The purpose of this study was to determine the relationship of two types of social support (emotional and instrumental) and two types of social undermining (critical appraisal and isolation) with five categories of alcohol, drug, or mental disorders (ADM; any mood, any anxiety, any substance abuse, any disorder, and two or more disorders) in 169 American Indian women presenting for primary care at an Indian Health Service facility. Social support and social undermining are often treated as opposite poles, but in fact they are distinct factors with independent effects. The findings illustrate that social support and undermining variables have a significant relationship with ADM outcomes even when controlling for confounding demographic variables. Any substance abuse was associated with all four social variables, while two or more disorders were associated with instrumental support and isolation. Any anxiety (isolation), any mood (critical appraisal), and any disorder (isolation) were each associated with one social variable. Overall, social undermining appears to have a stronger relationship with mental health than with social support.