Abstract Background Patients with acute leukemia experience a substantial symptom burden and are at risk of developing infections throughout the course of repeated cycles of intensive chemotherapy. Physical activity in recent years has been a strategy for rehabilitation in cancer patients to remedy disease and treatment related symptoms and side effects. To date, there are no clinical practice exercise guidelines for patients with acute leukemia undergoing induction and consolidation chemotherapy. A randomized controlled trial is needed to determine if patients with acute leukemia can benefit by a structured and supervised counseling and exercise program. Methods/design This paper presents the study protocol: Patient Activation through Counseling and Exercise – Acute Leukemia (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with acute leukemia (35 patients/study arm) following induction chemotherapy in the outpatient setting. Eligible patients will be randomized to usual care or to the 12 week exercise and counseling program. The intervention includes 3 hours + 30 minutes per week of supervised and structured aerobic training (moderate to high intensity 70 - 80%) on an ergometer cycle, strength exercises using hand weights and relaxation exercise. Individual health counseling sessions include a self directed home walk program with a step counter. The primary endpoint is functional performance/exercise capacity (6 minute walk distance). The secondary endpoints are submaximal VO2 max test, sit to stand and bicep curl test, physical activity levels, patient reported outcomes (quality of life, anxiety and depression, symptom prevalence, intensity and interference). Evaluation of clinical outcomes will be explored including incidence of infection, hospitalization days, body mass index, time to recurrence and survival. Qualitative exploration of patients’ health behavior and experiences. Discussion PACE-AL will provide evidence of the effect of exercise and health promotion counseling on functional and physical capacity, the symptom burden and quality of life in patients with acute leukemia during out patient management. The results will inform clinical practice exercise guidelines and rehabilitation programs for patients undergoing treatment for acute leukemia. Optimizing the treatment and care pathway may ease the transition for patients from illness to the resumption of everyday activities. Trial registration ClinicalTrials.gov Identifier: NCT01404520.