Late life depression is widely associated with lower quality of life and greater disability, making it an important target for prevention. Earlier randomized controlled trials [RCTs] demonstrated that speed of processing training [SOPT] led to reductions in depressive symptoms and clinical depression in community-dwelling adults. Our purpose was to evaluate depression outcomes related to SOPT among older adults who live in supported senior living settings. This two-arm, parallel RCT included 351 participants aged 55–102 years who resided in assisted and independent settings in 31 senior living communities. Participants were randomized within sites to computerized SOPT vs. computerized crossword puzzles with a targeted dose of 10 hours of playtime at baseline plus 4 hours of booster training at five and eleven months. Depression outcomes included the 9-item Patient Health Questionnaire [PHQ-9] scores, categorical levels, and dichotomous indicators. Random effects linear mixed effect models estimated SOPT effects in intention-to-treat complete case and multiple imputation analyses. Mean age of the sample was 81.0 years, 72.2% were women, and 41.0% resided in assisted living. At baseline 65.7% had no depression [PHQ-9 scores < 5] and 6.6% had clinically meaningful depression [PHQ-9 scores ≥ 10]. At 12 months we found significantly increased PHQ-9 scores [p = 0.006] and categorical levels [p = 0.003], and higher percentages of PHQ-2 scores > 3 [p = 0.016] and major depressive syndrome [p = 0.045] among the assisted living SOPT group. No significant change in depression was observed in the independent living SOPT or attention control groups. In summary, the SOPT known as Road Tour/Double Decision significantly increased, rather than decreased, the burden of depressive symptoms among participants residing in assisted living. Given these risks, this SOPT program should be avoided among older people in assisted living settings, and other SOPT interventions should be combined with systematic depression monitoring.