Objectives We estimate the causal impact of intensive caregiving, defined as providing at least 80 hours of care per month, and work, on the mental health of caregivers while considering possible sources of endogeneity in these relationships. Methods We use two linked data sources from the U.S. by matching caregivers in the National Study of Caregiving (NSOC) with corresponding care recipients in the National Health and Aging Trends Study (NHATS) for years 2011-2017. We address possible sources of endogeneity in the relationships between caregiving, work and mental health by using instrumental variables methodology, instrumenting for both caregiving and work behavior. We examine two measures used to screen for depression (PHQ-2 psychodiagnostic test) and anxiety (GAD-2 generalized anxiety disorders screening instrument), a composite measure that combines these measures (PHQ-4), and positive well-being variables to ascertain possible gains from caregiving. Results Providing at least 80 hours of care per month to a parent compared to less intensive caregiving increases the PHQ-4 Scale for anxiety and depression disorders. This is driven by the screening score for anxiety and not psycho-diagnostics test scores for depression. Relationship quality decreases substantially for intensive caregivers, and intensive caregiving leads to less satisfaction that the care recipient is well-cared for. We do not find offsetting mental health gains for intensive caregivers compared to non-intensive caregivers. Work does not independently impact mental health of caregivers. Discussion Caregiver interventions that reduce objective demands or support intensive caregivers could reduce or prevent well-being losses and improve caregiver’s relationship with the recipient.