Depression often accompanies chronic illness. Study aims included determining (1) the level of current depression (Patient Health Questionnaire (PHQ)-8≥10) for two sets of Chronic Disease Self-Management Programs (CDSMP) participants; (2) if depression or other outcomes improved for those with PHQ-8≥10; and (3) if outcomes differed for participants with or without depression. This study utilized longitudinal secondary data analysis of depression cohorts (PHQ-8≥10) from two independent translational implementations of the CDSMP, small-group (N=175) and Internet-based (N= 110). At baseline, 27 and 55 % of the two samples had PHQ-8 10 or greater. This decreased to 16 and 37 % by 12 months (p<0.001). Both depressed and nondepressed cohorts demonstrated improvements in most 12-month outcomes (pain, fatigue, activity limitations, and medication adherence). The CDSMP was associated with long-term improvements in depression regardless of delivery mode or location, and the programs appeared beneficial for participants with and without depression.