Little is known about the comorbidity of alcohol use, anxiety, hopelessness, and trauma among Mexican Americans, especially those living in impoverished and often isolated communities or neighborhoods (colonias in Spanish) along the U.S.-Mexico border that may be particularly vulnerable due to stressful living conditions. The current study utilized a community participatory model to investigate the relationships of alcohol use, acculturation, anxiety, hopelessness, and trauma in 100 Mexican origin colonia residents. Significant comorbidity was expected and that anxiety, hopelessness, and post-traumatic symptoms were hypothesized to be associated with the severity of the alcohol use disorders of participants. Participants who met DSM-IV criteria for alcohol dependence reported significantly more symptoms of anxiety and post-traumatic stress, and symptoms of anxiety were significantly associated with alcohol use disorders. This study provides evidence of the need for further investigation of stress, trauma, anxiety, hopelessness, and alcohol abuse in Mexican American residents and to inform future prevention and treatment efforts to improve both the physical and mental health of this population.