It has been proposed that cumulative stress, one's experience of chronic stressors across multiple domains, worsens health by altering the extent to which daily stressors impact daily affect and physical symptoms. Recent work confirms that high cumulative stress exacerbates the association between daily stressor exposure and increased daily negative affect, though it remains untested the extent to which cumulative stress and daily stressor exposure interact to predict daily symptoms. We employed data from the second wave of the midlife in the U.S. Survey (N = 2,022; Mage = 56.2; 57.2% female) to examine whether levels of cumulative stress compound daily symptoms on days with (vs. without) stressful events. Experiences of life stressors across eight domains, occurrence of daily stressors, and occurrence, number, and severity of daily physical symptoms were analyzed using multilevel modeling. Greater cumulative stress and experiencing (vs. not experiencing) a daily stressor independently increased the odds of occurrence, number, and severity of daily symptoms (ps ≤ .016). Moreover, after adjusting for covariates (e.g., sociodemographic characteristics, chronic health conditions, percent of days with reported stressors, and health behaviors), the associations between daily stressor exposure and odds of occurrence, number, and severity of daily symptoms were potentiated as levels of cumulative stress increased (ps ≤ .009). The negative implications of daily stressor exposure for daily health may be most pronounced in those who report higher levels of cumulative stress across multiple life domains and across time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).