Acute and chronic stress have been reported to have differing effects on physical activity in rodents, but no study has examined a chronic stress protocol that incorporates stressors often experienced by rodents throughout a day. To examine this, the effects of the Unpredictable Chronic Mild Stress (UCMS) protocol on voluntary running wheel activity at multiple time points, and/or in response to acute removal of chronic stress was determined. Twenty male Balb/c mice were given access and accustomed to running wheels for 4 weeks, after which they were randomized into 2 groups; exercise (EX, n = 10) and exercise with chronic stress using a modified UCMS protocol for 7 hours/day (8:00 a.m.-3:00p.m.), 5 days/week for 8 weeks (EXS, n = 10). All mice were given access to running wheels from approximately 3:30 p.m. to 7:30 a.m. during the weekday, however during weekends mice had full-time access to running wheels (a time period of no stress for the EXS group). Daily wheel running distance and time were recorded. The average running distance, running time, and work each weekday was significantly lower in EXS compared to EX mice, however, the largest effect was seen during week one. Voluntary wheel running deceased in all mice with increasing age; the pattern of decline appeared to be similar between groups. During the weekend (when no stress was applied), EXS maintained higher distance compared to EX, as well as higher daily distance, time, and work compared to their weekday values. These results indicate that mild chronic stress reduces total spontaneous wheel running in mice during the first week of the daily stress induction and maintains this reduced level for up to 8 consecutive weeks. However, following five days of UCMS, voluntary running wheel activity rebounds within 2-3 days.