At a time when serious xenophobic and heterosexist sentiment is at the forefront of our country’s political climate, it is incredibly important to explore and understand the links between discrimination and mental health for vulnerable communities. The purpose of this study was to carry out a preliminary exploration of the relations between acculturation to the United States (U.S.), discrimination related to ethnic minority and sexual minority statuses, and mental health symptomatology (depression, posttraumatic stress disorder [PTSD], and substance abuse) of sexual minority women who have emigrated to the U.S. from Latin America. A total of 152 women were recruited across the continental U.S. via online and in-person recruitment methods. As hypothesized, findings revealed that increased discrimination was associated with increased symptomatology of depression, PTSD, and substance abuse. However, acculturation was not shown to be associated with mental health for this sample. Recommendations for clinical practice and future research are discussed.