© 2016, Society of Behavioral Medicine. Depression and stress have been associated with less weight loss among some participants in behavioral weight loss (BWL) programs. The purpose of this study was to (1) measure the levels of depression and stress among a sample of black women living in rural Alabama and Mississippi who were participating in a BWL program and (2) examine the association between these psychosocial variables and weight loss outcomes of participants at 6 months. Overweight and obese black women in a BWL program (n = 409) completed validated surveys to measure depression and stress at baseline and 6 months. Weight and height were also measured at baseline and 6 months. Statistical tests were conducted to examine associations between depression, stress, and weight loss. Mean BMI at baseline was 38.68 kg/m2. Participants achieved a 1.17 kg/m2 reduction in BMI at 6 months. When comparing by baseline depression or stress categories, no significant differences in weight loss outcomes were observed. Analysis of continuous data revealed a significant correlation between baseline depression score and change in BMI. In adjusted models, change in depression score over time was significantly associated with change in weight. No differences in weight loss outcomes at 6 months were observed when comparing participants with and without elevated depressive symptoms or elevated stress at baseline. This suggests that potential participants may not need to be excluded from BWL programs based on pre-specified cut points for these psychological conditions. Greater improvements in depression were associated with better weight loss outcomes suggesting that more emphasis on reducing depression may lead to greater weight losses for black women in BWL programs.