Addressing caregiver depression is of high public health importance due to its ties with overall wellbeing, risk for cardiovascular diseases (CVD), and ability to sustain caregiving duties. To improve the impact of caregiver interventions, it is essential to understand the mechanisms through which interventions achieve reductions in depression and CVD risk, as well as the caregiving situation-related factors that may impact treatment response. The current study employed a data analytic focus on mediators and moderators of a previously completed randomized clinical trial of the Pleasant Events Program (PEP), a behavioral activation intervention. A sample of Alzheimer's Disease spousal caregivers (N = 98 74% female) was randomized to either PEP or to a timeequivalent Informational Support control condition. PEP emphasized pleasant events scheduling and reductions in avoidance behaviors (i.e., lack of engagement in activities) in the context of ongoing caregiver responsibilities; the Informational Support intervention emphasized supportive listening and providing information. Participants were assessed at baseline and at 6-weeks. Co-primary outcomes were depression as measured by the Center for Epidemiologic Studies-Depression Scale and CVD risk marker interleukin-6. Higher levels of interleukin-6 are implicated in inflammatory processes, constituting higher risk for CVD. Multiple regression models and the Monte Carlo Method for Assessing Mediation were used to test change in pleasant events, activity restriction, and personal mastery as mediators of depression after PEP. Moreover, depression was tested as a mediator between PEP and reductions in interleukin-6. Secondly, models were used to investigate constructs measured via standardized assessments (e.g., care recipient disruptive behaviors) as moderators of PEP outcomes. The current study found that change in personal mastery, activity restriction, and pleasant activities were not significant mediators of change in depression after PEP. Moreover, changes in depression did not mediate changes in cardiovascular risk marker interleukin- 6. Caregiver social support, current number of working status, vulnerability, and disruptive behaviors of care recipients did not significantly moderate treatment response. Moderators of response to PEP and mediators that account for changes in depression and CVD risk after PEP are still unknown. Future intervention studies should utilize oversampling methods to investigate mediators and moderators of post-treatment depression and interleukin-6 change.