We report a field study examining within-individual effects of workload on distress at work and daily well-being. The study was conducted using experience-sampling methodology to measure daily workload, affective distress, and blood pressure throughout and at the end of each of 10 workdays, and emotional burnout and daily strain (two indicators of low well-being) during the evening in a sample of 64 full-time employees who provided a total of 354 person-day data points. We also measured employees’ job control and perceived organizational support with a separate survey. Results showed that workload was positively associated with affective distress and blood pressure, and with the indicators of low daily well-being. Furthermore, affective distress mediated the relationship between workload and daily well-being. More importantly, job control and organizational support had cross-level moderating influences on the relationships of workload with affective distress and blood pressure such that these relationships were weaker for participants who reported having more control on their job, as well as for participants who reported receiving more organizational support.