Purpose: A single-arm trial evaluated the feasibility, acceptability, and outcomes of COPE-D, a collaborative care intervention for underserved cancer patients with depression. Methods: Bilingual (Spanish and English) care managers provided counseling and/or medication management in consultation with physicians. Outcomes were treatment improvement (‚â• 5-point reduction in PHQ-9), treatment response (‚â• 50% reduction in PHQ-9), suicidal ideation resolution, and changes in depression (PHQ-9), anxiety (GAD-2), sleep disturbance (PSQI), global mental and physical health (PROMIS), social isolation (PROMIS), and qualitative feedback. Results: 193 patients consented to participate. 165 initiated and 141 completed treatment, with 65% and 56% achieving treatment improvement and response, respectively. Outcomes did not differ by ethnicity (31% Hispanic), cancer stage (71% stages III-IV), income, or education. Suicidal ideation, depression, anxiety, sleep disturbance, and social isolation also improved. Qualitative feedback was largely positive. Conclusion: COPE-D improved depression and quality of life among underserved patients, with acceptable retention rates. Keywords: Patient Health Questionnaire Anxiety and Depression Scale; cancer; depression; oncology; psychosocial intervention; sleep.