Minority women often have a unique set of beliefs and expectations about medical treatment. At this time, there is a dearth of research looking at how depressed minority women respond to pharmacological interventions for the sexual concomitants of depression. This was the first study to examine the impact of a medication switch, from a selective serotonin reuptake inhibitor to bupropion SR, on the sexual functioning of depressed minority women. Eighteen minority women (5 Hispanic, 10 African American, 2 Asian American, and 1 Native American), who were experiencing poor tolerability and/or lack of efficacy on an adequate trial of a selective serotonin reuptake inhibitor for depression, along with low sexual desire, were enrolled in this prospective open-label study. The selective serotonin reuptake inhibitor and bupropion SR were cross-tapered with a target dose of 150 to 300 mg of bupropion SR. The patients were followed for 10 weeks, and measures of sexual functioning and depression (Hamilton Rating Scale for Depression) were administered in an academic medical setting. Data were collected from July 2003 to December 2004. In the group as a whole, there were significant improvements in desire (F1,17 = 34.86, P < 0.001), arousal (F1,17 = 25.99, P < 0.001), and orgasm (F1,17 = 20.16, P < 0.001), on the Changes in Sexual Functioning Questionnaire. African-American women demonstrated the greatest improvement in depression (F1,16 = 9.55, P = 0.006), desire (F1,16 = 8.62, P = 0.01), and arousal (F1,16 = 8.83, P = 0.009) after the medication switch. Overall, this intervention appeared to be an effective treatment of low sexual desire in a diverse group of depressed minority women. The majority of women successfully completed the trial and planned to continue using bupropion SR after their participation in the study.