Acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation is treated with corticosteroids, placing patients at risk for steroid myopathy. In this single-arm cohort study, 23 patients who were started on high-dose corticosteroids for acute graft-versus-host disease underwent a series of functional tests (baseline and days 14, 28, and 56): 6-min walk test, hip flexor and knee extensor strength via dynamometry, five times sit-to-stand, Brooke scale for myopathy, modified Adult Myopathy Assessment Tool, and manual muscle testing. Participants were prescribed home exercises including walking and resistance exercises, with low adherence. Fifteen (63%) participants were male and median (range) age was 60 (36–70) yrs. Median (range) corticosteroid duration and cumulative equivalent methylprednisolone dose were 66 (22–165) days and 3625 (1020–11720) mg, respectively. At day 14, there was a significant decline in five times sit-to-stand (P = 0.0132), knee extensor (P = 0.0182), and manual muscle testing (P = 0.0466). Functional tests negatively associated with cumulative corticosteroid dose included 6-min walk test distance (P = 0.0103), hip flexor strength (P = 0.0262), knee extensor strength (P = 0.0369), and manual muscle testing strength (P = 0.0319). Five times sit-to-stand was positively associated with corticosteroid dose (P = 0.0003). In conclusion, stem cell transplant patients receiving high-dose corticosteroids for acute graft-versus-host disease are at risk for weakness detected as early as day 14. Increasing adherence to exercise may mitigate these changes.