Background Mental health disorders can potentially decrease quality of life and survival in patients with cancer. Little is known about the survival implications of mental health disorders in patients with diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the effect of pre-existing depression, anxiety, or both on survival in a US cohort of older patients with DLBCL. Methods Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients aged 67 years or older, diagnosed with DLBCL in the USA between Jan 1, 2001, and Dec 31, 2013. We used billing claims to identify patients with pre-existing depression, anxiety, or both before their DLBCL diagnosis. We compared 5-year overall survival and lymphoma-specific survival between these patients and those without pre-existing depression, anxiety, or both using Cox proportional analyses, adjusting for sociodemographic and clinical characteristics, including DLBCL stage, extranodal disease, and B symptoms. Findings Among 13 244 patients with DLBCL, 2094 (15 center dot 8%) had depression, anxiety, or both disorders; 6988 (52 center dot 8%) were female, and 12 468 (94 center dot 1%) were White. The median follow-up for the cohort was 2 center dot 0 years (IQR 0 center dot 4-6 center dot 9 years). 5-year overall survival was 27 center dot 0% (95% CI 25 center dot 1-28 center dot 9) for patients with these mental health disorders versus 37 center dot 4% (36 center dot 5-38 center dot 3) for those with no mental health disorder (hazard ratio [HR] 1 center dot 37, 95% CI 1 center dot 29-1 center dot 44). Although survival differences between mental health disorders were modest, those with depression alone had the worst survival compared with no mental health disorder (HR 1 center dot 37, 95% CI 1 center dot 28-1 center dot 47), followed by those with depression and anxiety (1 center dot 23, 1 center dot 08-1 center dot 41), and then anxiety alone (1 center dot 17, 1 center dot 06-1 center dot 29). Individuals with these pre-existing mental health disorders also had lower 5-year lymphoma-specific survival, with depression conferring the greatest effect (1 center dot 37, 1 center dot 26-1 center dot 49) followed by those with depression and anxiety (1 center dot 25, 1 center dot 07-1 center dot 47) and then anxiety alone (1 center dot 16, 1 center dot 03-1 center dot 31). Interpretation Pre-existing depression, anxiety, or both disorders present within 24 months before DLBCL diagnosis, worsens prognosis for patients with DLBCL. Our data underscore the need for universal and systematic mental health screening for this population, as mental health disorders are manageable, and improvements in this prevalent comorbidity might affect lymphoma-specific survival and overall survival. Funding American Society of Hematology, National Cancer Institute, Alan J Hirschfield Award. Copyright (c) 2023 Elsevier Ltd. All rights reserved.