Objective: To examine the association between early HIV viremia and mortality after HIV-associated lymphoma. Design: Multicenter observational cohort study. Setting: Center for AIDS Research Network of Integrated Clinical Systems cohort. Participants: HIV-infected patients with lymphoma diagnosed between 1996 and 2011, who were alive 6 months after lymphoma diagnosis and with at least two HIV RNA values during the 6 months after lymphoma diagnosis. Exposure: Cumulative HIV viremia during the 6 months after lymphoma diagnosis, expressed as viremia copy-6-months. Main outcome measure: All-cause mortality between 6 months and 5 years after lymphoma diagnosis. Results: Of 224 included patients, 183 (82%) had non-Hodgkin lymphoma (NHL) and 41 (18%) had Hodgkin lymphoma. At lymphoma diagnosis, 105 (47%) patients were on antiretroviral therapy (ART), median CD4+ cell count was 148 cells/μl (interquartile range 54-322), and 33% had suppressed HIV RNA (<400 copies/ml). In adjusted analyses, mortality was associated with older age [adjusted hazard ratio (AHR) 1.37 per decade increase, 95% CI 1.03-1.83], lymphoma occurrence on ART (AHR 1.63, 95% CI 1.02-2.63), lower CD4+ cell count (AHR 0.75 per 100 cells/μl increase, 95% CI 0.64-0.89), and higher early cumulative viremia (AHR 1.35 per log10copies × 6-months/ml, 95% CI 1.11-1.65). The detrimental effect of early cumulative viremia was consistent across patient groups defined by ART status, CD4 + cell count, and histology. Conclusion: Exposure to each additional 1-unit log10 in HIV RNA throughout the 6 months after lymphoma diagnosis was associated with a 35% increase in subsequent mortality. These results suggest that early and effective ART during chemotherapy may improve survival. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.