Associations between various forms of activity engagement (e.g. work, leisure) and the experience of stress in workers have been widely documented. The mechanisms underlying these effects, however, are not fully understood. Our goal was to investigate if perceived whole day workload accounted for the relationships between daily frequencies of activities (i.e. work hours and leisure/rest) and daily stress. We analysed data from 56 workers with type 1 diabetes (T1D) who completed approximately two weeks of intensive longitudinal assessments. Daily whole day workload was measured with an adapted version of the National Aeronautics and Space Administration Task Load Index (NASATLX). A variety of occupations were reported, including lawyer, housekeeper and teacher. In multilevel path analyses, day-to-day changes in whole day workload mediated 67% (p < .001), 61% (p < .001), 38% (p < .001), and 55% (p < .001) of the within-person relationships between stress and work hours, rest frequency, active leisure frequency, and day of week, respectively. Our results provided evidence that whole day workload perception may contribute to the processes linking daily activities with daily stress in workers with T1D. Perceived whole day workload may deserve greater attention as a possible stress intervention target, ones that perhaps ergonomists would be especially suited to address.