This research examined the relationship between negative self-perceptions and sexual risk behavior in a sample of 156 heterosexually identified, methamphetamine users from San Diego, California. The Beck Depression Inventory and the Self Esteem Rating Scale, respectively, were used to assess depression and negative self-perceptions. Measures of sexual risk behavior and methamphetamine use were developed specifically for this research. Data were gathered in 2001-2002. Participants were primarily male (76%), Caucasian (56%), never married (51%), and unemployed (73%), with a mean age of 39.1 years. Participants with high levels of negative self-perceptions evidenced the greatest degree of sexual risk behavior, including significantly more unprotected vaginal sex and a larger number of sexual partners as compared to individuals with low levels of negative self-perceptions. In cross-sectional analyses, negative self-perceptions predicted intensity of methamphetamine use and depressive symptoms. However, neither of these variables were found to mediate the relationship between negative self-perceptions and sexual risk behavior. Findings are discussed in relation to the need for further research into the role of negative self-perceptions as a determinant of sexual risk behavior among methamphetamine users.