Given the burden of depression among those with HIV, and the impact of HIV on urban minority communities there is an urgent need to assess innovative treatment interventions that not only treat depression but do so in a way that allows for increased access to mental health care. This single site, uncontrolled, pilot study sought to determine the feasibility and depression outcomes of an 11-session telephone-based cognitive behavioral therapy intervention delivered over 14 weeks targeting low-income, urban-dwelling, HIV-infected African-American people with major depression. The diagnosis of major depression was made using the Mini International Neuropsychiatric Interview. The primary outcome was the Hamilton Depression Rating Scale (HAM-D) and the secondary outcome was the Quick Inventory of Depression Symptomatology-Self Report (QIDS-SR). Feasibility and satisfaction were also assessed. Assessments occurred at baseline, midpoint and at study conclusion (14 weeks). Fifteen people were screened for the study. Six HIV-infected, low-income, African-American people individuals (five females and one male) were eligible and participated in the study. All patients finished the study. On average, participants completed nine sessions. The sessions lasted for an average of 48 min (SD = 11.5). Compared to mean HAM-D score at baseline (HAM-D = 22.8 (SD = 3.1), the mean HAM-D score was significantly reduced at study conclusion (HAM-D = 9.8 (SD = 7.4); (t (5) = 4.6, p = 0.006); (Cohen d = 1.9)). Compared to the mean QIDS-SR score at baseline (QIDS-SR = 15.5 (SD = 4.2) the mean QIDS score was significantly reduced at study conclusion (QIDS = 7.0 (SD = 5.4);(t (5) = 3.2, p = 0.02); (Cohen d = 1.3)).The mean satisfaction scores across all participants at post-treatment was 5.7 (SD = 0.3) with of a maximum score of 6. Telephone-based CBT can be delivered to low-income, urban-dwelling ethnic minority HIV-infected people resulting in significant reductions in depression symptoms with high satisfaction. The efficacy of this intervention will be assessed in a planned randomized control trial.