Objectives: This research documents spousal accounts of daily symptoms and behaviors of their husbands or wives with mild cognitive impairment (MCI) and assesses how MCI-related symptoms and care needs are associated with spouse care partners’ psychological well-being and biomarkers of physiological wear and tear. Method: Thirty spouse care partners participated in a 7-day diary study and reported on behavior problems associated with MCI as well as daily stressors and strains they experienced. They also provided saliva samples on 4 of the study days. Results: Multilevel models revealed daily variability and change in psychological affect and the diurnal cortisol rhythm. Daily primary stressors, everyday secondary strains, and marital interactions predicted these changes. Discussion: The findings document the negative physiological effects of having a spouse with MCI and provide new details on probable causes of psychological and biological distress. They shed light on MCI-specific interventions to address couples’ needs before severe disease progression occurs that could interfere with spouses’ ability to provide home-based care and support.